
Protected: OCULAR (COMING SOON)
November 18, 2023
CERAMIDE BLOCKER (Lipotoxicity Neutralizer)
February 9, 2024INTRODUCING
INTERSTELLAR BLEND™
triglyceride
DECIMATOR
200:1 Concentration
scienTIFIC EVIDENCE
Lowering triglycerides can have several effects on obesity
1. Improved lipid metabolism: Obesity is often associated with dyslipidemia, which is characterized by elevated levels of triglycerides in the blood. Lowering triglyceride levels can help restore normal lipid metabolism, reducing the risk of obesity-related complications such as cardiovascular diseases and liver steatosis.
2. Reduced fat accumulation: High levels of triglycerides can contribute to the accumulation of fat in adipose tissue and other organs. By lowering triglyceride levels, the body is less likely to store excess fat, which can help prevent further weight gain and promote weight loss.
3. Enhanced insulin sensitivity: Obesity is closely linked to insulin resistance, a condition in which cells become less responsive to the effects of insulin. Elevated triglyceride levels can impair insulin signaling and worsen insulin resistance. Lowering triglycerides can improve insulin sensitivity, allowing for better glucose uptake and utilization by cells, which can help manage obesity and prevent the development of type 2 diabetes.
4. Reduced inflammation: Obesity is associated with chronic low-grade inflammation, which can contribute to the development of metabolic disorders. Elevated triglyceride levels can promote inflammation in adipose tissue and other organs. Lowering triglycerides can help reduce inflammation, potentially improving metabolic health and reducing obesity-related complications.
It is important to note that while lowering triglycerides can have beneficial effects on obesity, it is just one aspect of a comprehensive approach to managing and treating obesity. Lifestyle modifications, including a healthy diet, regular physical activity, and weight management, are also crucial for long-term success in managing obesity.
Methods: This was an observational study using data from the National Health and Nutrition Examination Survey (2005–2018), a cross-sectional and nationally representative database. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). TyG index was calculated based on the equation as follows: ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2], and participants were divided into quartiles based on TyG index. Weighted multivariable logistic regression models were used to explore the relationship between the TyG index and depression.
Results: A total of 13,350 patients were included, involving 1001 (7.50%) individuals with depression. Higher TyG index is significantly associated with elevated depressive symptoms in U.S. adults. Multivariate-adjusted HRs for patients in the TyG index 4th quartile were higher for depression (OR = 1.46; 95% confidence interval (CI) 1.30, 1.64) compared with the 1st quartile of TyG index. Similar results were seen in men and women, across age groups, and baseline comorbidities.
Conclusion: In this large cross-sectional study, our result suggests that population with higher TyG index are significantly more likely to have depressive symptoms in U.S. adults.
Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function
In obese individuals, atherogenic dyslipidemia is a very common and important factor in the increased risk of cardiovascular disease. Adiposity-associated dyslipidemia is characterized by low high-density lipoprotein cholesterol (HDL-C) levels and an increase in triglyceride-rich lipoproteins. Several factors and mechanisms are involved in lowering HDL-C levels in the obese state and HDL quantity and quality is closely related to adiponectin levels and the bioactive lipid sphingosine-1-phosphate.
Recent studies have shown that obesity profoundly alters HDL metabolism, resulting in altered HDL subclass distribution, composition, and function. Importantly, weight loss through gastric bypass surgery and Mediterranean diet, especially when enriched with virgin olive oil, is associated with increased HDL-C levels and significantly improved metrics of HDL function. A thorough understanding of the underlying mechanisms is crucial for a better understanding of the impact of obesity on lipoprotein metabolism and for the development of appropriate therapeutic approaches. The objective of this review article was to summarize the newly identified changes in the metabolism, composition, and function of HDL in obesity and to discuss possible pathophysiological consequences.
Postulated effects of obesity on adiponectin and HDL metabolism. In normal-weight subjects, adipocytes produce adiponectin, which enhances expression of the ATP-binding cassette transporter A1 (ABCA1) through activation of peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor alpha (LXRα), leading to HDL assembly. Further, adiponectin increases the hepatic production of apoA-I. During the state of obesity, adipocytes manifest several altered properties, which play a role in the reduction of HDL-C. Increased inflammation and fat accumulation in the adipocytes reduces the production of adiponectin and impairs cholesterol flux to HDL. The reduction of adiponectin downregulates apoA-I production and ABCA1 expression in hepatocytes, thus reducing HDL assembly.
Metabolic syndrome (MetS), also known as syndrome X, ‘insulin resistance syndrome’, and hypertriglyceridemic waist, is a clustering of obesity, hyperglycemia, insulin resistance, and dyslipidemia. MetS increases the risk of developing atherosclerotic cardiovascular disease (CVD) and is now considered one of the most important cardiovascular risk factors.
Obesity and Hypertriglyceridemia Produce Cognitive Impairment
High triglyceride levels can cause cognitive impairment through several mechanisms:
1. Impaired synaptic plasticity: Triglycerides can impair the maintenance of the NMDA component of hippocampal long-term synaptic potentiation (LTP). LTP is a process involved in the strengthening of synaptic connections, which is crucial for learning and memory. When triglyceride levels are elevated, the maintenance of LTP is compromised, leading to cognitive impairments.
2. Oxidative stress: High levels of triglycerides can contribute to oxidative stress in the brain. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses. This oxidative stress can damage neurons and impair cognitive function.
3. Leptin resistance: Triglycerides can also contribute to leptin resistance, which is a condition where the brain becomes less responsive to the hormone leptin. Leptin plays a role in regulating appetite and metabolism, but it also has important functions in the brain, including cognitive processes. When there is leptin resistance, the brain does not receive the necessary signals for proper cognitive function, leading to impairments.
The most critical factor in obesity that causes cognitive impairment is elevated triglyceride levels. Studies have shown that hypertriglyceridemia, or high levels of triglycerides in the blood, directly and immediately affect cognition. Obese individuals with hypertriglyceridemia exhibit impaired cognitive performance compared to those with normal triglyceride levels. Lowering triglyceride levels through interventions has been shown to improve cognitive impairments in obese individuals. Additionally, triglycerides impair the maintenance of NMDA-dependent hippocampal long-term synaptic potentiation, which is considered a neurophysiological correlate of learning and memory.
ingredients
13-oxo-9,11-octadecadienoic acid
In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitroexperiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic Triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.
3,5,6,7,8,3′,4′-heptamethoxyflavone
Oil Red O staining was used to observe the accumulation of lipids and foam cell formation. As shown in Figure 3A, the number of red lipid droplets was significantly increased, and the lipid droplets were distributed in a ring-like pattern within the ox-LDL-induced RAW264.7 cells, which indicated that the foam cell model was successfully established. Incubation with TAN, HxMF, and HpMF significantly reversed such consequences. In addition, the contents of Triglyceride and TC were quantitatively tested. As expected, the levels of Triglyceride and TC were significantly increased by ox-LDL stimulation (Figures 3B,C). TAN (12, 25, and 50 μM) significantly reduced Triglyceride levels in a dose-dependent manner. The Triglyceride content was significantly reduced by HxMF (25 and 50 μM) and HpMF (50 μM) treatments. All three PMFs showed significant inhibition of TC levels in ox-LDL-induced RAW264.7 cells.
6-Gingerol
Excessive synthesis of Triglycerides and cholesterol accelerates the progression of hepatic steatosis in metabolic-associated fatty liver disease (MAFLD). However, the precise mechanism by which 6-gingerol mitigates hepatic steatosis in MAFLD model mice has yet to be fully understood. The present study observed that 6-gingerol administration exhibited significant protective effects against obesity, insulin resistance, and hepatic steatosis in mice subjected to a high-fat diet (HFD), and mitigated lipid accumulation in HepG2 cells treated with palmitate (PA). Following the hepatic lipidomic analysis, we confirmed that the AMPK-SREBPs signaling pathway as the underlying molecular mechanism by which 6-gingerol inhibited Triglyceride and cholesterol biosynthesis, both in vivo and in vitro, through Western blot and immunofluorescence assay.
Additionally, the application of an AMPK agonist/inhibitor further validated that 6-gingerol promoted AMPK activation by increasing the phosphorylation level of AMPK in vitro. Notably, the inhibitory effect of 6-gingerol on cholesterol biosynthesis, rather than Triglyceride biosynthesis, was significantly diminished after silencing SREBP2 using a lentiviral plasmid shRNA in HepG2 cells. Our study demonstrates that 6-gingerol mitigates hepatic Triglyceride and cholesterol biosynthesis to alleviate hepatic steatosis by activating the AMPK-SREBPs signaling pathway, indicating that 6-gingerol may be a potential candidate in the therapy of MAFLD.
We investigated the effects of 6-gingerol on adiposity and obesity-induced inflammation by focusing on the regulation of adipogenesis and adipokines in white adipose tissue (WAT) of diet-induced obese mice. C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% 6-gingerol for 8 weeks. 6-Gingerol supplementation significantly reduced body weight, WAT mass, serum Triglyceride , leptin and insulin levels, and HOMA-IR in HFD-fed mice.
Additionally, the size of adipocytes in epididymal fat pads was reduced in HFD-fed mice by 6-gingerol supplementation. 6-Gingerol reduced the mRNA and protein levels of adipogenesis-related transcription factors, such as SREBP-1, PPARγ, and C/EBPα in WAT. Furthermore, 6-gingerol suppressed the expression of lipogenesis-related genes, such as fatty acid synthase and CD36 in WAT. Adiponectin expression was significantly increased, whereas inflammatory adipokines (leptin, resistin, TNF-α, MCP-1, and PAI-1) and the macrophage marker F4/80 were significantly reduced in the WAT of HFD-fed mice by 6-gingerol supplementation. In conclusion, 6-gingerol effectively contributed to the alleviation of adiposity and inflammation in WAT, which is associated with the regulation of adipokines in diet-induced obese mice.
9-oxo-10(E),12(E)-octadecadienoic acid
Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo.
In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic Triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.
Acacia senegal Seeds
Acacia senegal L. (Fabaceae) seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), Triglycerides, and VLDL-cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed.
Apart from reduced atherosclerotic plaques in aorta () and increased lumen volume (), administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, Triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics.
Effect of Gum Arabic (Acacia senegal, L. Willd) on lipid profile and performance of Laying Hens
Objective: This experiment studied effect of Gum Arabic as a supplementary diet and its effect on lipid profile (serum, egg yolk and meat) and performance of Laying Hen. Methodology and results: One hundred and fifty commercial laying hens (29 weeks age/ white lohmann) were used. The 150 laying hens are divided into five groups randomly G1, G2, G3, G4 and G5, where each group contained 30 laying hens kept in separated battery house. G1(Control) was fed basal layers diet while G2, G3, G4 and G5 were fed basal diet supplemented with Gum Arabic concentration at 1, 3, 5 and 7% respectively. The study revealed that in serum, there was a significant decrease in cholesterol, Triglyceride , but no significant difference in High Density protein (HDP) – cholesterol at P≤ 0.05, in egg yolk.
There was a significant decrease in cholesterol for G5 compared with G1, also there was a significant decrease Triglyceride in G4 and G5 compared with G1 indicated that there was a decrease in phospholipids in G5 compared with G1. Lipid profile of meat for treated groups (G2, G3, G4 and G5) showed no significant difference at P≤ 0.05 compared with non- treated group (G1). The performance (body weight, egg weight and daily egg production) of laying hens showed significant increase at P≤ 0.05, but there was an increase in body and egg weight. Finally, there was no significant difference in daily egg production at P≤ 0.05. The addition of Gum Arabic as supplement of laying hens diet indicated there was no significant difference in serum cholesterol and daily egg production. Whereas, it is showed significant decrease in Triglyceride , total lipid and phospholipids, but indicated significant increase in egg and body weight. Application of Gum Arabic as supplement in the diet of poultry production should be done because Gum Arabic is rich in highly soluble fiber.
The prevailing strategy for the management of hypercholesterolemia is the use of HMG-CoA reductase inhibitors which work by inhibiting cholesterol synthesis by HMG-CoA reductase in the liver and removal of excess cholesterol level in peripheral circulation by several mechanisms of reverse cholesterol transport [47, 48]. Excess cholesterol in the circulatory system is indicated by biomarker indices of dyslipidaemia and abnormal lipoproteins ratios, which can be regulated by proper fractional esterication of cholesterol and reverse cholesterol transport (RCT) [49, 50]. Cholesterol present in the intestine is rst absorbed in the form of chylomicron (Triglyceride rich complex) and is then modied and packaged as high-density lipoprotein (HDL) cholesterol. Therefore, the ratio of Triglyceride to HDL is indicative of the levels of peripheral cholesterol in circulation.
Abnormal cholesterol esterication rates in apoB-lipoprotein- depleted plasma (fractional esterication) and lipoprotein particle size result in dyslipidaemia [49, 51]. In animal model, specically hypercholesteraemic rabbits, exhibit elevated levels of the biomarker indices of dyslipidaemia, such as the logarithm of the TG/HDL ratio, total cholesterol/ HDL (Castelli risk index -I (CRI-I)) and LDL-cholesterol/HDL-cholesterol (Castelli risk index-II (CRI-II)). In the present study, the treatment of hypercholesterolemic rabbits with an aqueous seed extract of Acacia senegal (L.) Willd. caused a signicant reduction in the atherogenic index and CRI – I&II, indicating improved fractional esterication of cholesterol and reverse cholesterol transport.
Achillea millefolium L.extract
Background: Recent studies have reported that herbal extracts may have some protectiveeffect against the complications of diabetes mellitus. This study aimed to investigate theeffects of Achillea millefolium hydroalcoholic extract in comparison to metformin on liver damage,lipid abnormality, and glycemic control in diabetic rats.
Methods: Rats were randomly assigned to 7 groups of 10 animals. Diabetes was induced by injection of streptozotocin (STZ) to 4 groups of rats. Three groups of diabetic rats were given 250 mg/kg/day metformin, 25 mg/kg/day Achillea millefolium hydroalcoholic extract, or 100 mg/kg/day of this extract. Two non-diabetic groups were also given either 25 mg/kg/day or 100 mg/kg/day Achillea millefolium extract. Normal control and diabetic control rats received 1 mL/day of normal saline. Treatments were administered through oral gavage for 28 days. At the end, rats were anesthetized with ether and theirserum samples were separated in order to measurebloodglucose,serum total protein,lipids, and liver enzymes.
Results: There was a significant reduction inbloodglucose,serum liver enzymes, Triglycerides , and total- andLDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterolserum level in the Achillea millefolium-treated groups.
Conclusion: Achillea millefolium extract compared to metformin reduceslipid abnormality,bloodglucose and liver enzymes in STZ-induced diabetic rats. Future clinical studies are warranted to confirm our experimental findings in humans.
Background: Recent studies have reported that herbal extracts may have some protective effect against the complications of diabetes mellitus. This study aimed to investigate the effects of Achillea millefolium hydroalcoholic extract in comparison to metformin on liver damage, lipid abnormality, and glycemic control in diabetic rats.
Methods: Rats were randomly assigned to 7 groups of 10 animals. Diabetes was induced by injection of streptozotocin (STZ) to 4 groups of rats. Three groups of diabetic rats were given 250 mg/kg/day metformin, 25 mg/kg/day Achillea millefolium hydroalcoholic extract, or 100 mg/kg/day of this extract. Two non-diabetic groups were also given either 25 mg/kg/day or 100 mg/kg/day Achillea millefolium extract. Normal control and diabetic control rats received 1 mL/day of normal saline. Treatments were administered through oral gavage for 28 days. At the end, rats were anesthetized with ether and their serum samples were separated in order to measure blood glucose, serum total protein, lipids, and liver enzymes.
Results: There was a significant reduction in blood glucose, serum liver enzymes, Triglycerides, and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.
Conclusion:Achillea millefolium extract compared to metformin reduces lipid abnormality, blood glucose and liver enzymes in STZ-induced diabetic rats. Future clinical studies are warranted to confirm our experimental findings in humans.
Achillea sibirca extract
There was a significant reduction in blood glucose, serum liver enzymes, Triglycerides, and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.
Acorus calamus L.extract
Hypolipidemic Effect of Methanol Fraction of Acorus calamus Linn. in Diet-Induced Obese Rats
Acorus calamus Linn. is a traditional medicinal plant included in “lekhaneyagana” (which means “reduce excess fat”), a pharmacological classification mentioned by Charaka in Charakasamhita. Traditionally, this plant has been prescribed as a first-line treatment for many ailments such as digestive problems, diabetes, obesity, and related problems. The purpose of the present study was to check the effect of methanolic fraction of A. calamus on serum lipids, Lecithin-cholesterol acyltransferase (LCAT) enzyme, and apolipoproteins.
We found that treatment of A. calamus at concentrations of 200 and 400 mg/kg body weight was able to reduce total cholesterol (T-c), Triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) levels and increase high-density lipoprotein cholesterol (HDL-c) levels compared to model control group. A. calamus treatment results in activation of LCAT enzyme, which helps in the maturation of HDL-c. ApoA1 level was found to be increased considerably by the administration of A. calamus extract, and the Apo B level was decreased. GCMS analysis of the A. calamus extract showed the presence of compound, Friedelan-3-one. The result suggests the use of methanol fraction of A .calamus, as a potential drug for controlling the cholesterol level.
Agaricus blazei Mur ill extract
This study was performed to investigate the effects of liquid culture of Agaricus blazei on the lipid metabolism and enzyme activities in growing male rats. Sprague-Dawley rats were given four different types of diets for a succeeding period of 5 weeks, respectively a normal diet group (7% corn oil), a high fat diet group (7% com oil + 15% lard), a 20 or 30% Agaricus diet groups (high fat diet + 20 or 30% Agaricus in water) according to the levels of Agaricus supplementation. The body weight gains, food intake, food efficiency ratios, and hepatic, kidney, spleen and pancreas weights of the rats fed 20 or 30% Agaricus diets were similar to those of the rats fed high fat diet. The epididymal fat pad weight of the rats fed high fat diet and 20 or 30% Agaricus diets were significantly higher than that of the rats fed normal diet.
The concentrations of serum Triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol, and the activity of glutamic pyruvic transaminase in the rats fed 30% Agaricus diet were significantly lower than those in the rats 114 high fat diet. But the concentrations of hepatic total cholesterol and Triglyceride of rats fed the 20 or 30% Agaricus diets were similar to those of rats fed the high fat diet. The HDL-oholesterol/total-cholesterol ratio of the rat fed 30% Agaricus diet was significantly higher than that of the rats fed high fat diet, The activity of glutamic oxaloacetic transaminase in the rats fed 20 or 30% Agaricus diets were similar to those in the rats fed high fat diet. There were no differences in the concentrations of total protein, hemoglobin and glucose, and the activities of alkaline phosphatase, and the atherogenic index in the serum among the experimental groups. These results showed that the 30% Agaricus diet feeding decreased the total cholesterol, the Triglyceride and the LDL-cholesterol, and increased the HDL-oholesterol/total cholesterol ratio in serum of rats.
Obesity and diabetes mellitus are associated with common pathogenic mechanism, and ${\beta}-glucan$ of Agaricus blazei Murill is potent inhibitor of intestinal ${\alpha}-glycosidase$ and inhibit the digestion of starch and sucrose in the small intestine. In this studies, there was observed the anti-hyperglycemic effect in obese diabetic mice(C57BLKsJ db/db), which were supplied Agaricus and Acarbose for 5 weeks. In db/db mice, food intake and body weight gain were decreased significantly in Agaricus groups(p<0.05). Also these group exhibited lower fasting serum glucose level compared with control group. HbA1c level, Triglyceride level, total cholesterol level, HDL cholesterol level, LDL cholesterol level and VLDL cholesterol level were lowered in db/db mice. The activity of disaccharidases on proximal and distal segments of small intestine was decreased. In conclusion, it was assumed that ${\beta}-glucan$ of Agaricus blazei Murill has anti-hyperglycemic and anti-obesitic effects by reducing food intake and body weight gain, and also decreasing serum glucose and lipid level through inhibiting the activity of small intestinal disaccharidases.
Ajuga iva extract
Diabetes is also associated with hyperlipidaemia (i.e. high levels of plasma total cholesterol, LDL-C and triglycerides and low plasma HDL-C)[33] which plays an important role in the development of premature atherosclerosis. Indeed, in STZ-induced diabetic rats, a significant increase of serum LDL-C and very-low-density lipoprotein (VLDL)-C and reduction in HDL-C compared with normal control rats were noted.[34] High total cholesterol level is one of the major risk factors for coronary heart diseases,[35] constituting the main cause of morbi-mortality in diabetes mellitus.[36]
The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL2-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney.
Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent triglyceride and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.
Alfalfa extract Total Flavonoids
The two last groups orally received aqueous extract of alfalfa for 21 days. At the end of experiment, sugar, cholesterol, Triglycerides, high-density and low-density lipoprotein, and aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels were measured in the samples. Consumption of aqueous alfalfa extract significantly reduced glucose, cholesterol, Triglycerides, and low-density lipoprotein (LDL) levels in the diabetic rats but enhanced high-density lipoprotein (HDL) levels. ALT and AST liver enzyme levels were also reduced in blood. Histological examination showed that the aqueous alfalfa extract caused reconstruction of damaged liver and enhanced Langerhans islets’ diameter in pancreas. Therefore, all signs of diabetes were improved by oral administration of alfalfa in defined dose.
Alisma orientalis (Sam.) Juzep.extract
Alisma orientale (Sam.) Juzep (A. orientale) is a traditional herb that is often used to treat disease including edema and hyperlipidemia. However, the molecular mechanism by which Alisma orientale (Sam.) Juzep exerts itshypolipidemiceffects remains unclear. In this study, a diabetic rat model was established by feeding ahigh-fat andhigh-sugardiet combined with a low-dose streptozotocin injection (HFS). Then the rats were treated with an A. orientale water extract (AOW), an A. orientale ethanolic extract (AOE) or metform (MET). The gut microflora and liver transcriptome were analyzed byhigh-throughput next-generation sequencing. Ultra-performance liquid chromatography-triple quadrupole-mass spectrometry was employed to analyze the major compounds in the AOE. The results showed that theserum totalcholesterol (TC) and low density lipoproteincholesterol (LDL-C) levels in rats of the AOE group (2.10 g/kg/day, 14 days) were significantly lower than those in the HFS group (p<0.01).
Moreover, AOE treatment altered the gut microecology, particularly modulating the relative abundance of gut microflora involved inlipidmetabolism compared with the HFS group. Furthermore, compared with the HFS group, the mRNA expression levels of Fam13a, Mapk7, Mpp7, Chac1, Insig1, Mcpt10, Noct, Greb1l, Fabp12 and Hba-a3 were upregulated after the administration of AOE. In contrast, the mRNA expression levels of Lox, Mybl1, Arrdc3, Cyp4a2, Krt20, Vxn, Ggt1, Nr1d1 and S100a9 were downregulated. Moreover, AOE treatment for two weeks markedly promoted the relative abundance of Lachnospiraceae (p = 0.0013). The triterpenoids contents in AOE were alisol A, alisol A 24-acetate, alisol B, alisol B 23-acetate, alisol C 23-acetate, alisol F, alisol F 24-acetate, and alisol G. Our findings above illustrated that thehypolipidemiceffect of the triterpenoids of A. orientale is mediated mainly through alteration of the gut microecology and the regulation of genes involved incholesterolmetabolism, especially Insig1.
Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging hepatic manifestation of metabolic syndrome. However, its unrevealed mechanism and complicated comorbidities have led to no specific medication, except for weight loss and lifestyle modification. Alisma orientale (Sam.) Juzep (A. orientale, Alismataceae) has been increasingly reported on therapeutic effects of A. orientale against NAFLD and metabolic syndrome such as insulin resistance, hyperlipidemia, and obesity. Therefore, this study aimed to review the preclinical efficacy of A. orientale and its chemical constituents including Alisol A 24-acetate, Alisol B 23-acetate, Alisol F, and Alismol against NAFLD and metabolic syndrome. A. orientale prevented hepatic Triglyceride accumulation through suppressing de novo lipogenesis and increasing lipid export. In addition, it controlled oxidative stress markers, lipoapoptosis, liver injury panels, and inflammatory and fibrotic mediators, eventually influencing steatohepatitis and liver fibrosis.
Moreover, it exhibited pharmacological activities against hyperlipidemia, obesity, and hyperglycemia as well as appetite. These biological actions of A. orientale might contribute to adiponectin activation or a role as a farnesoid X receptor agonist. In particular, Alisol A 24-acetate and Alisol B 23-acetate could be expected as main compounds. Taken together, A. orientale might be an effective candidate agent for the treatment of NAFLD and its comorbidities, although further assessment of its standardization, safety test, and clinical trials is consistently required.
The treatment of cardiovascular diseases and obesity, two diseases posing a major risk to human health, has been plagued by the scarcity of potent and effective medication with fewer side effects. To address this problem, numerous efforts, and some progress, have been made. Among possible treatments are some medicinal herbs; particularly promising is Alisma orientale (AO). In the last decade, an increasing amount of research has shown that AO has some desirable therapeutic effects on cardiovascular diseases and obesity. Because of its efficacy, natural origin, and minimal adverse effects, AO has aroused great attention. Based on this, this review provides an overview of the latest progress from the last decade regarding the pharmacological and therapeutic effects, molecular mechanisms, and related effective constituents of AO in the treatment of cardiovascular diseases and obesity.
Results from the research currently available reveal that active constituents of AO, such as alisol B 23-acetate, alisol A 24-acetace, and alisol A, have been proven to be effective for treating cardiovascular diseases by modulating the lipid metabolism of macrophages, improving the biological behavior of vascular smooth muscle cells (VSMCs), and enhancing anti-inflammatory effects. Moreover, the active constituents of AO can also intervene in obesity by modulating abnormal glucose and lipid metabolism and fat decomposition of the body by activating the AMPK- and PPAR-related signaling pathways. In summation, based upon our research of available literature, this review reveals that AO and its active constituents have a great potential to be used as drugs for treating cardiovascular diseases and ameliorating obesity.
Allicin
Cholesterol-Lowering Effect of Allicin on Hypercholesterolemic ICR Mice
Allicin was discussed as an active compound with regard to the beneficial effects of garlic in atherosclerosis. The aim of this study was to investigate the cholesterol-lowering properties of allicin. In order to examine its effects on hypercholesterolemia in male ICR mice, this compound with doses of 5, 10, or 20 mg/kg body weight was given orally daily for 12 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of serum cholesterol, Triglyceride, glucose, and hepatic cholesterol storage were determined.
Following a 12-week experimental period, the body weights of allicin-fed mice were less than those of control mice on a high-cholesterol diet by 38.24 ± 7.94% (P < 0.0001) with 5 mg/kg allicin, 39.28 ± 5.03% (P < 0.0001) with 10 mg/kg allicin, and 41.18 ± 5.00% (P < 0.0001) with 20 mg/kg allicin, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Meanwhile, allicin showed a favorable effect in reducing blood cholesterol, Triglycerides, and glucose levels and caused a significant decrease in lowering the hepatic cholesterol storage. Accordingly, both in vivo and in vitro results demonstrated a potential value of allicin as a pronounced cholesterol-lowering candidate, providing protection against the onset of atherosclerosis.
Allium cepavar. aggregatum G. Don extract
effect of the polyphenol-rich extract from Allium cepa on hyperlipidemic sprague-dawley rats
Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such asAtherosclerosis in the folk. This study was mainly aimed at investigating theeffects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of totalcholesterol (TC), Triglyceride (TG), low-density lipoproteincholesterol (LDL-C),high-density lipoproteincholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity inserum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyzeLDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42 mg/g DW) and isoquercitrin (4.60 mg/g DW) were the main constituents of ACE using HPLC analysis.
Furthermore, ACE reduced the levels of TC, TG,LDL-C, and MDA, and increased HDL levels and elevated SOD activity both inserum and liver in hyperlipidemic SD rats (p < .05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and thelipid and foam cells of the aortic arch of the rats in ACE group were markedlyameliorated. WB results showed that ACE promoted the degradation of HMGCR and increasedLDLR expression in liver (p < .05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation ofLDLR. PRACTICAL APPLICATIONS:Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, duringAtherosclerosis development, hyperlipidemia is an important risk factor.
To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the sideeffects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such asAtherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation ofLDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statinlipid-lowering agent.
Studies on Antihyperliperlipemic and Antioxidant Activity of Allium cepa L.
This Study was attempted to investigate the effect of Allium cepa L. (onion) on the activities of GOT and GPT, the levels total lipids, Triglyceride , total cholesterol, phospholipid and ${\beta}-lipoprotein$ in the serum and the increase ratio of body and liver weight in the experimentally induced hyperlipemic rats. The activities of S-GOT and S-GPT were significantly decreased in dose of onion juice 3 ml and 5 ml/head as compared to the high lipid-diet control group. The levels of total lipids. Triglyceride , total cholesterol and phospholipids were significantly decreased in dose of onion juice 3 ml and 5 ml/head as compared to the control group, respectively. However, the level of ${\beta}-lipoprotein$ was significantly decreased in dose of onion juice 3 ml/head.
The levels of Triglyceride and total cholesterol in the liver were significanatly decreased in dose of onion juice 3 ml/head. Increase ratio of the body and liver weight were significantly decreased in dose of onion juice 3 ml/head. Anti-fatigue activity of onion juice were studied in mice using the swimming performance method. The potencies of anti-fatigue acti-vities was significantly found in 1.2 ml/head. p.o. of onion juice. The methanol extract and juice extract of onion was significantly found to have an antioxidative activity on the air oxidation of linoleic acid as compared to the 3-butyl-4-hydroxyanisole and ${\alpha}-tocopherol$.
Allium sativum extract
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
A 12-week intervention with KRG was conducted in patients with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed with T2DM. Subjects were randomized in a double-blind, placebo-controlled trial. The trial results showed that 12 weeks of intervention with KRG supplementation (5 g/day) led to normalization of whole blood and serum glucose levels as well as serum insulin and CRP concentrations (Bang et al., 2014). Administration of Panax Ginseng extract (PGE) for 8 weeks (6 g/day) decreased serum triglycerides and total cholesterol and LDL levels, while increasing HDL levels.
These results were attributed to PGE potent antioxidant effects (Kim and Park, 2003). In accordance, the effects of a low-dose (3 g/day) and a high-dose (6 g/day) of KRG supplementation for 8 weeks on antioxidant enzymes and oxidative stress markers in humans were assessed in a randomized, double-blind, placebo-controlled trial. Increased GSH-Px, SOD, and CAT activities were found in the high-dose group as compared to the placebo group. Plasma oxidized-LDL levels and DNA tail length and tail moment were significantly decreased in both high and low dose groups but increased in the placebo group. This led to the conclusion that supplementation with KRG upregulates antioxidant enzymes activities and consequently attenuates lymphocyte DNA damage (Lee et al., 2012).
cholesterollowering property of garlic (Allium sativum) on patients with hypercholesterolemia
Background: Cardiovascular disease especially atherosclerotic coronary heart disease (CHD) accounts for a large population of all deaths and disability worldwide. Elevatedlipid levels have a strong association with cardiovascular events. Objectives: Study aim is to reducecholesterol levels with garlic supplementation. Materials and Methods: It is a prospective, interventional open-label study to see theeffect of garlic onserumcholesterol levels. Study was conducted in the Department of Pharmacology and Therapeutics, Rajendra Institute of Medical Sciences, Ranchi. Fifty Healthy subjects with elevatedcholesterol levels between 240 and 330 mg/dL were enrolled. Subjects were given 3 g of raw garlic daily for a total period of 90 days.
Follow-up was done on 30th, 60th, and 90th day after starting treatment. Results: In male patients, theserumcholesterol level showed significant decrease of 13% (P < 0.001) from mean baseline of 269.30 mg/dL to 233.93 mg/dL at 90th day. In female patients, the decrease was 10% (P < 0.001) from mean baseline of 260.30 mg/dL to 233.90 mg/dL at 90th day. Conclusion: Garlic has a role incholesterol management as an adjunctive therapy in most cases of significant hypercholesterolemia therebyreducing risk ofAtherosclerosis and cardiovascular events.
A review on the effects of Allium sativum (Garlic) in metabolic syndrome
The metabolic syndrome is a common problem world-wide and includes abdominal obesity, hypertension, dyslipidemia, and hyperglycemia disorders. It leads to insulin resistance and the development of diabetes mellitus or cardiovascular disease. Allium sativum (garlic) has been documented to exhibit anti-diabetic, hypotensive, and hypolipidemic properties.
This suggests a potential role of A. sativum in the management of metabolic syndrome; however, more studies should be conducted to evaluate its effectiveness. In this review, we discussed the most relevant articles to find out the role of A. sativum in different components of metabolic syndrome and cardiovascular disease risk factors. Because human reports are rare, further studies are required to establish the clinical value of A. sativum in metabolic syndrome.
alpha-Linolenic acid
Alpha-linolenic acid (ALA) reduces cardiovascular disease (CVD) risk, possibly by favorably changing vascular inflammation and endothelial dysfunction. Inflammatory markers andlipids and lipoproteins were assessed in hypercholesterolemic subjects (n = 23) fed 2diets low in saturated fat andcholesterol, andhigh in PUFA varying in ALA (ALAdiet) and linoleic acid (LAdiet) compared with an average Americandiet (AAD). The ALAdiet provided 17% energy from PUFA (10.5% LA; 6.5% ALA); the LAdiet provided 16.4% energy from PUFA (12.6% LA; 3.6% ALA); and the AAD provided 8.7% energy from PUFA (7.7% LA; 0.8% ALA). The ALAdiet decreased C-reactive protein (CRP, P < 0.01), whereas the LAdiet tended to decrease CRP (P = 0.08).
Although the 2high-PUFAdiets similarly decreased intercellular cell adhesion molecule-1 vs. AAD (-19.1% by the ALAdiet, P < 0.01; -11.0% by the LAdiet, P < 0.01), the ALAdiet decreased vascular cell adhesion molecule-1 (VCAM-1, -15.6% vs. -3.1%, P < 0.01) and E-selectin (-14.6% vs. -8.1%, P < 0.01) more than the LAdiet. Changes in CRP and VCAM-1 were inversely associated with changes inserum eicosapentaenoic acid (EPA) (r = -0.496, P = 0.016; r = -0.418, P = 0.047), or EPA plus docosapentaenoic acid (r = -0.409, P = 0.053; r = -0.357, P = 0.091) after subjects consumed the ALAdiet. The 2high-PUFAdiets decreasedserum totalcholesterol,LDLcholesterol and Triglycerides similarly (P < 0.05); the ALAdiet decreased HDLcholesterol andapolipoprotein AI compared with the AAD (P < 0.05). ALA appears to decrease CVD risk by inhibiting vascular inflammation and endothelial activation beyond itslipid-lowering effects.
This meta-analysis aimed to investigate the impact of low-ratio linoleic acid/alpha-linolenic acid (LA/ALA) supplementation on the blood lipid profiles in adults. We conducted a systematic search for relevant randomized controlled trials (RCTs) assessing the effects of low-ratio LA/ALA using databases including PubMed, Embase, Cochrane, and Web of Science, as well as screened related references up until February 2023. The intervention effects were analyzed adopting weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis indicated that low-ratio LA/ALA supplementation decreased total cholesterol (TC, WMD: −0.09 mmol/L, 95% CI: −0.17, −0.01, p = 0.031, I2 = 33.2%), low-density lipoprotein cholesterol (LDL-C, WMD: −0.08 mmol/L, 95% CI: −0.13, −0.02, p = 0.007, I2 = 0.0%), and Triglycerides (TG, WMD: −0.05 mmol/L, 95% CI: −0.09, 0.00, p = 0.049, I2 = 0.0%) concentrations.
There was no significant effect on high-density lipoprotein cholesterol concentration (HDL-C, WMD: −0.00 mmol/L, 95% CI: −0.02, 0.02, p = 0.895, I2 = 0.0%). Subgroup analysis showed that low-ratio LA/ALA supplementation significantly decreased plasma TC, LDL-C, and TG concentrations when the intervention period was less than 12 weeks. In the subgroup analysis, a noteworthy decrease in both TC and LDL-C levels was observed in individuals receiving low-ratio LA/ALA supplementation in the range of 1–5. These findings suggest that this specific range could potentially be effective in reducing lipid profiles. The findings of this study provide additional evidence supporting the potential role of low-ratio LA/ALA supplementation in reducing TC, LDL-C, and TG concentrations, although no significant impact on HDL-C was observed.
Amaranthus viridis leaf extract
Hypercholesterolemia is one of the main causes for coronary heart disease, which occurs due tohigh levels ofserumcholesterol.oxidizedLDL accumulation leads to atherosclerotic plaque formation, which contributes to myocardial infarction and cardiovascular diseases. Consumption of statins leads to adverse healtheffects such as liver and muscle toxicity; thus attention is now focused on alternative treatments using chemicals of plant origin. This study is designed to investigate the phytochemical components,hypocholesterolemic andAntiatheroscleroticeffects of Amaranthus viridis (A. viridis) using hypercholesterolemic rabbits. Gas Chromatography Mass Spectrometry (GC-MS/MS) analysis revealed 30 compounds, whilereverse Phase-high Performance Liquid Chromatography (RP-HPLC) detected the presence of ascorbic acid, rutin, quercetin and catechin. An animal model study was performed on twenty New Zealand white rabbits that were randomly divided into 5 groups and fed with normaldiet, 2%highcholesteroldiet (HCD), 2% HCD + 10 mg kg−1 simvastatin, 2% HCD + 100 mg kg−1 A. viridis extract and 2% HCD + 200 mg kg−1 A. viridis extract, respectively.
The supplementation with A. viridis extract significantly reduced totalcholesterol,LDL and Triglyceride levels, and increased the levels of HDL and antioxidant enzymes (SOD and GPx). The elevated levels of AST, ALT and creatine kinase indicate liver and muscle injuries. Treatment with A. viridis extract also diminished the development of aortic plaques and decreased the intima : media ratio, as observed in simvastatin-treated rabbits. The phytocomponents of A. viridis have been reported to have therapeuticeffects in treating hypercholesterolemia andAtherosclerosis, and the in vivo study on A. viridis further confirms its potential as an alternative therapeutic agent.
Hypercholesterolemia is one of the main causes for coronary heart disease, which occurs due to high levels of serum cholesterol. Oxidized LDL accumulation leads to atherosclerotic plaque formation, which contributes to myocardial infarction and cardiovascular diseases. Consumption of statins leads to adverse health effects such as liver and muscle toxicity; thus attention is now focused on alternative treatments using chemicals of plant origin. This study is designed to investigate the phytochemical components, hypocholesterolemic and antiatherosclerotic effects of Amaranthus viridis (A. viridis) using hypercholesterolemic rabbits.
Gas Chromatography Mass Spectrometry (GC-MS/MS) analysis revealed 30 compounds, while Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) detected the presence of ascorbic acid, rutin, quercetin and catechin. An animal model study was performed on twenty New Zealand white rabbits that were randomly divided into 5 groups and fed with normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg kg−1 simvastatin, 2% HCD + 100 mg kg−1 A. viridis extract and 2% HCD + 200 mg kg−1 A. viridis extract, respectively. The supplementation with A. viridis extract significantly reduced total cholesterol, LDL and Triglyceride levels, and increased the levels of HDL and antioxidant enzymes (SOD and GPx). The elevated levels of AST, ALT and creatine kinase indicate liver and muscle injuries.
To investigate the antihyperglycemic and hypolipidemic effects of methanolic extract of leaves of Amaranthus viridis (MEAV) in normal and Streptozotocin (STZ) induced diabetic rats. The anti-hyperglycemic and hypolipidemic activity of methanolic extract of leaves of Amaranthus viridis was evaluated by using normal and STZ induced diabetic rats at dose of 200 mg/kg and 400 mg/kg by mouth per day for 21 days. Blood glucose levels and body weight was monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum Triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed.
The statistical data indicated a significant increase in the body weight, decrease in the blood glucose, total cholesterol and serum Triglycerides after treatment with MEAV. High density lipoprotein (HDL) cholesterol level was significantly increased when treated with extract. Histologically, focal necrosis was observed in the diabetic rat pancreas; however, was less obvious in treated groups. The MEAV has beneficial effects in reducing the elevated blood glucose level and body weight changes, and improves the lipid profile of STZ induced rats.
Amomum subulatum seeds (Family Zingiberaceae)
In the present study, hypolipidemic activity of fraction (50:50; CHCl3:CH3OH) of Amomum subulatum (Zingiberaceae) seeds was evaluated incholesterol-fed rabbits. Hyperlipidemia induced by feeding atherogenicdiet for 120 days resulted in a significant increase inserum totalcholesterol, phospholipid and Triglyceride levels when compared with control group. The levels ofLDL and VLDL-cholesterol were increased significantly, but the HDL-cholesterol ratio was decreased. The changes in the antioxidant parameters were accompanied by an increase inlipid peroxidation and reduction in glutathione (GSH) and catalase activity.
The level oflipid peroxidation was reduced whereas GSH content and catalase activity were elevated after the treatment with A. subulatum fraction at the dose level of 100 mg/kg.b.wt/day. A significant reduction was observed in totalcholesterol, Triglyceride , phospholipid,LDL and VLDLcholesterol where as HDL-cholesterol ratio was increased after administration of A. subulatum. The results of the present study indicate that fraction of A. subulatum possesseslipid-lowering and antioxidant activity and could be beneficial in the treatment of hyperlipidemia.
In the present study, hypolipidemic activity of fraction (50:50; CHCl3:CH3OH) of Amomum subulatum (Zingiberaceae) seeds was evaluated in cholesterol-fed rabbits. Hyperlipidemia induced by feeding atherogenic diet for 120 days resulted in a significant increase in serum total cholesterol, phospholipid and Triglyceride levels when compared with control group. The levels of LDL and VLDL-cholesterol were increased significantly, but the HDL-cholesterol ratio was decreased. The changes in the antioxidant parameters were accompanied by an increase in lipid peroxidation and reduction in glutathione (GSH) and catalase activity.
The level of lipid peroxidation was reduced whereas GSH content and catalase activity were elevated after the treatment with A. subulatum fraction at the dose level of 100 mg/kg.b.wt/day. A significant reduction was observed in total cholesterol, Triglyceride , phospholipid, LDL and VLDL cholesterol where as HDL-cholesterol ratio was increased after administration of A. subulatum. The results of the present study indicate that fraction of A. subulatum possesses lipid-lowering and antioxidant activity and could be beneficial in the treatment of hyperlipidemia.
Ananas comosus
Background: Pineapple peel is a waste component of pineapple with valuable source of metabolites as phytoactive compounds in ameliorating metabolic-related disorders. This study investigated the atheroprotective and neuroprotectiveeffects of peel extract of Ananas comosus fruit (PEAC) in normaldiet (ND) andhigh-fatdiet (HFD) fed rats.
Methods: Male Wistar rats were fed ND or HFD for 9 weeks, and beginning from the 6th week animals were also orally treated with PEAC (200 mg/kg). Memory performance was assessed using Y-maze test (YMT) and novel object recognition test (NORT) while anxiolytic-likeeffect was assessed on the elevated plus maze (EPM).serumcholesterol, Triglycerides and HDL-C were determined, whileLDL-C and atherogenic risk calculated.serum and brain tissue malondialdehyde, reduced glutathione, catalase were determined. Brain acetylcholinesterase activity and interleukin-6 level were also determined.
Results: PEAC significantly attenuated HFD-induced reduction in correct alternation in YMT, and discrimination index in NORT. Also, PEAC demonstrated anxiolytic-like activity in EPM test. PEAC significantlyimprovedlipid profile and decreased risk of atherogenicity in ND and HFD-fed rats. In addition, PEAC improvesserum and brain antioxidant status by decreasing malondialdehyde and increasing GSH and catalase. PEAC significantly impaired HFD-induced brain acetylcholinesterase activity and IL-6 levels.
Conclusion: These findings suggest that peel extract of Ananas comosus fruit may protect againstdiet-induced behavioral disturbances via atheroprotective, antioxidants and anti-inflammatory activities.
In this study, we investigated hypolipidemic mechanisms of the ethanolic extract of Ananas comosus L. leaves (AC) in mice and then determined its activities in related enzymes. The results showed that AC (0.40 g/kg) significantly inhibited the increase in serum Triglycerides by 40% in fructose-fed mice. In mice induced by alloxan and high-fat diets, serum total cholesterol remained at a high level (180 – 220 mg/dl) within 7 days of removing high-fat diets but reached normal level (120 – 140 mg/dl) after AC (0.40 g/kg per day) treatment. Also, AC (0.40 and 0.80 g/kg) significantly inhibited serum lipids from the increase in Triton WR-1339-induced hyperlipidemic mice. AC (0.01 – 100 µg/ml) selectively activated lipoprotein lipase (LPL) activity by 200% – 400% and significantly inhibited 3-hydroxyl-methyl glutaryl coenzyme A (HMGCoA) reductase activity by 20% – 49% in vitro.
Furthermore, 2 months of fenofibrate (0.20 g/kg) administration particularly increased mice liver weights (0.0760 ± 0.0110 g/g) while AC (0.40 g/kg) had no effect (0.0403 ± 0.0047). Taken together, these results suggest that AC will be a new potential natural product for the treatment of hyperlipidemia that exerts its actions through mechanisms of inhibiting HMGCoA reductase and activating LPL activities. Its action mechanisms differentiate from those with fibrates but may be partly similar to those with statins. It is hopeful that AC may serve as the adjuvant for fibrates.
andrographolide
Triglyceride Andrographolide, a natural anti-inflammatory agent: An Update
Andrographolide can reduce liver Triglyceride content and liver macrophage infiltration and reduce the expression of proinflammatory and profibrotic genes in the liver in mice with nonalcoholic steatohepatitis. It can also inhibit NF-κB activity and the activity of the NLRP3 inflammasome in high-fat HepG2 cells to reduce liver inflammation and fibrosis (Cabrera et al., 2017).
A study has shown that in hepatic stellate cells, andrographolide can effectively reduce liver inflammation and fibrosis by suppressing the activity of the TLR4/NF-κB and TGF-β1/Smad2 signalling pathways (Lin et al., 2018). 14-Deoxy-11,12-didehydroandrographolide partially ameliorated steatohepatitis, liver fibrosis and liver injury in high-fat, high-cholesterol diet-induced fatty liver disease by enhancing hepatic Nrf2-mediated downstream antioxidant enzyme activity and inhibiting NLRP3 inflammasome activation, which can down-regulate the expression of NLRP3, Caspase-1 and IL-1β, and this anti-inflammatory property may be achieved by inhibiting the NF-κB signaling pathway.
Angelica sinensis (Oliv.) Diels.extract
Background: Angelica root is the dry root of the Umbelliferae plant Angelica sinensis (oliv) Diels. Angelica organic acid (OA) is the main active ingredient in Angelica sinensis, and it exerts potentialAnti-atheroscleroticeffects by preventingoxidized low-density lipoprotein (Ox-LDL) induced endothelial injury. To study the protectiveeffects of OA on ox-LDL-induced HUVECs autophagic flux dysfunction and inflammatory injury.
Methods: OA were isolated by water extraction and alcohol precipitation, and then the content of ferulic acid (FA) in the OA was determined byhigh performance liquid chromatography. The ox-LDL-induced endothelial injury model was established. Theeffect of ferulic acid on the survival of Human umbilical vein endothelial cells (HVUECs) was detected by CCK-8 assay. HUVECs were pretreated with different concentrations of OA (20 μmol/L, 40 μmol/L, and 80 μmol/L), and Western Blot was used to detect the expressions of LC3II, p62, MCP-1, VCAM-1 and LOX-1. The autophagosomes in HUVECs were observed by transmission electron microscopy (TEM).
Results: 20 μmol/L OA could increase the expression of LC3II and decrease the expression of p62, MCP-1, VCAM-1 and LOX-1. The results of TEM showed that angelica organic acids promoted cell organelle degradation in autolysosomes.
Conclusion: OA could reduce inflammation, protect endothelial cells and play anAnti-atherosclerotic role by enhancing the autophagy flux of damaged endothelial cells, in which FA the major active ingredient of OA played a major role.
In the present work, ASP with low MW was isolated via an optimized “one-step” purification process. The well-known traditional water extraction and alcohol precipitation methodology were adopted to acquire crude polysaccharides. Then, the crude extraction was purified by D315 weak-base ion-exchange resin which is believed to play an effective role in purification and absorption (Fan et al., 2018). After lyophilization, ASP (MW = 3.2 kDa) was obtained and subjected to free fatty acid (FFAs)-induced L02 cell lines in vitro.
It was speculated that ASP could decrease the level of triglyceride (TG) and total cholesterol (TC) level in supernatant. Also, through Oil Red O (ORO) and Nile red staining, ASP was postulated to ameliorate lipid accumulation in FFAs-induced cells. In order to investigate the lipid-lowering function of ASP in vivo, NAFLD model was established by feeding the ICR male mice (3–4 weeks) with HFD.
Annurca Apple Polyphenols
Background: Angelica root is the dry root of the Umbelliferae plant Angelica sinensis (oliv) Diels. Angelica organic acid (OA) is the main active ingredient in Angelica sinensis, and it exerts potentialAnti-atheroscleroticeffects by preventingoxidized low-density lipoprotein (Ox-LDL) induced endothelial injury. To study the protectiveeffects of OA on ox-LDL-induced HUVECs autophagic flux dysfunction and inflammatory injury.
Methods: OA were isolated by water extraction and alcohol precipitation, and then the content of ferulic acid (FA) in the OA was determined byhigh performance liquid chromatography. The ox-LDL-induced endothelial injury model was established. Theeffect of ferulic acid on the survival of Human umbilical vein endothelial cells (HVUECs) was detected by CCK-8 assay. HUVECs were pretreated with different concentrations of OA (20 μmol/L, 40 μmol/L, and 80 μmol/L), and Western Blot was used to detect the expressions of LC3II, p62, MCP-1, VCAM-1 and LOX-1. The autophagosomes in HUVECs were observed by transmission electron microscopy (TEM).
Results: 20 μmol/L OA could increase the expression of LC3II and decrease the expression of p62, MCP-1, VCAM-1 and LOX-1. The results of TEM showed that angelica organic acids promoted cell organelle degradation in autolysosomes.
Conclusion: OA could reduce inflammation, protect endothelial cells and play anAnti-atherosclerotic role by enhancing the autophagy flux of damaged endothelial cells, in which FA the major active ingredient of OA played a major role.
Aim: Cardiovascular disease (CVD) are among the main causes of death worldwide and dyslipidemias account for one of the risk factors for these diseases. Habitual apple consumption appears to be inversely associated with reduced cardiovascular risk. Then, this systematic review aims to investigate the effect of chronic apple consumption on the lipid profile of adults with dyslipidemia.
Methods: A systematic search was performed in electronic databases, including PubMed, Embase, Web of Science and Scopus, without restriction of year of publication. Inclusion criteria were randomized clinical trials in humans that investigated the effect of chronic consumption of whole fresh or dried apple, for a period longer than two weeks of intervention on the lipid profile.
Results: Based on the methodology used and following the pre-established search strategies, 4,468 articles were found. After applying the inclusion and exclusion criteria, five articles were selected for qualitative evaluation, covering 522 adult participants of both sexes. Three randomized controlled trials included in this review demonstrated that there was a decrease in plasma total cholesterol (TC), Triglyceride and low-density lipoprotein cholesterol (LDL-c) concentrations, in addition to an increase in high-density lipoprotein cholesterol (HDL-c) concentration. Two other studies found different results. Low risk of bias was identified in three studies.
Conclusions: The analysis of the studies indicates that the consumption of fresh and/or dried apples with the peel has a beneficial effect on the lipid profile of adults, with a decrease in TC and LDL-c. These effects may be related to polyphenols and soluble fibers, among other functional compounds present in this fruit.
Antrodia Camphorata
TT treatment dramatically lowered blood glucose levels by 34.2%~43.4%, which was comparable to the antidiabetic agent-Metf (36.5%). TT-treated mice reduced the HFD-induced hyperglycemia, hyper Triglyceride mia, hyperinsulinemia, hyperleptinemia, and hypercholesterolemia. Membrane levels of GLUT4 were significantly higher in CruE-treated groups in vitro. Skeletal muscle membrane levels of GLUT4 were significantly higher in TT-treated mice. These groups of mice also displayed lower mRNA levels of glucose-6-phosphatase (G6 Pase), an inhibitor of hepatic glucose production.
The combination of these agents produced a net hypoglycemic effect in TT-treated mice. TT treatment enhanced the expressions of hepatic and skeletal muscle AMP-activated protein kinase (AMPK) phosphorylation in mice. TT-treated mice exhibited enhanced expression of hepatic fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and increased mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a). These mice also exhibited decreased expression levels of lipogenic fatty acid synthase (FAS) in liver and adipose tissue and reduced mRNA levels of hepatic adipocyte fatty acid binding protein 2 (aP2) and glycerol-3-phosphate acyltransferase (GPAT). These alterations resulted in a reduction in fat stores within the liver and lower Triglyceride levels in blood.
Our results demonstrate that TT is an excellent therapeutic approach for the treatment of type 2 diabetes and hyper Triglyceride mia.
The aim of this study was to examine the effects of dehydroeburicoic acid (TT) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were randomly divided into six groups and given orally by gavage TT (at three dosages), metformin (Metf), fenfibrate (Feno), or vehicle for 4 weeks. STZ-induced diabetic mice showed elevations in blood glucose levels (P < 0.001). TT treatment markedly decreased blood glucose levels by 42.6–46.5%. Moreover, STZ-induced diabetic mice displayed an increase in circulating Triglyceride (TG) and total cholesterol (TC) levels (P < 0.001 and P < 0.01, respectively) but a decrease in blood insulin and adiponectin levels (P < 0.01 and P < 0.05, respectively). These substances are also reversed by TT treatment, indicating TT ameliorated diabetes and dyslipidemia.
Membrane skeletal muscular expression levels of glucose transporter 4 (GLUT4) and expression levels of AMPK phosphorylation (phospho-AMPK) in both liver and skeletal muscle were reduced in STZ-induced diabetic mice, which normalized upon TT treatment and correction of hyperglycemia accompanied with a decrease in mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6 Pase), which was related to the inhibition of hepatic glucose production and attenuating diabetic state. In addition, TT also showed hypolipidemic effect by increasing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a) but decreasing expression levels of fatty acid synthase (FAS), which further contributed to a decrease in circulating TG levels. TT-treated mice displayed decreased SREBP2 mRNA levels and reduced blood TC levels. These findings strongly support that TT prevents diabetic and dyslipidemic states in STZ-induced diabetic mice evidenced by regulation of GLUT4, PPARα, FAS, and phosphorylation of AMPK.
The present study was designed to evaluate the protective effect of sulphurenic acid (SA), a pure compound from Antrodia camphorata, on diabetes and hyperlipidemia in an animal model study and to clarify the underlying molecular mechanism. Diabetes was induced by daily 55 mg/kg intraperitoneal injections of streptozotocin (STZ) solution over five days. Diabetic mice were randomly divided into six groups and orally gavaged with SA (at three dosages) or glibenclamide (Glib), fenofibrate (Feno) or vehicle for 3 weeks. Our findings showed that STZ-induced diabetic mice had significantly increased fasting blood glucose, glycated hemoglobin (HbA1C), plasma Triglyceride (TG), and total cholesterol (TC) levels (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) but decreased blood insulin, adiponectin, and leptin levels compared to those of the control group (p < 0.001, p < 0.001, and p < 0.001, respectively).
Administration of SA to STZ-induced diabetic mice may lower blood glucose but it increased the insulin levels with restoration of the size of the islets of Langerhans cells, implying that SA protected against STZ-induced diabetic states within the pancreas. At the molecular level, SA treatment exerts an increase in skeletal muscle expression levels of membrane glucose transporter 4 (GLUT4) and phospho-Akt to increase the membrane glucose uptake, but the mRNA levels of PEPCK and G6Pase are decreased to inhibit hepatic glucose production, thus leading to its hypoglycemic effect. Moreover, SA may cause hypolipidemic effects not only by enhancing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) with increased fatty acid oxidation but also by reducing lipogenic fatty acid synthase (FAS) as well as reducing mRNA levels of sterol regulatory element binding protein (SREBP)1C and SREBP2 to lower blood TG and TC levels. Our findings demonstrated that SA displayed a protective effect against type 1 diabetes and a hyperlipidemic state in STZ-induced diabetic mice.
Antrodia cinnamomea
Antrodia cinnamomea is a Taiwanese medicinal mushroom with multiple pharmacological activities. Antrodia cinnamomea solid-state cultivated mycelium (LAC) exerts health-relatedeffects in animal and cell models, but clinical data is limited. This study aimed to determine the safety andeffects of LAC on human physiological functions. In an open-label, single-arm study, 32 healthy men and women ingested LAC capsules for three months. The subjects were monitored during the study and one month after the study end-point. LAC consumption did not significantly change fastingbloodglucose,blood pressure, and Triglyceride levels or liver and renal function indices. No adverse events occurred during the trial. Moreover, a significant change from baseline in totalcholesterol levels was observed; men and women had decreases of 5.7% and 5.3%, respectively. Based on these, the ingestion of LAC-capsule has a considerable degree of safety and has the potential to reduce total cholesterol in healthy adults.
Evaluation of Blood Lipid-Lowering Effects of Antrodia cinnamomea Mycelia Powder Complex
Objective: This study was conducted to assess the prenatal developmental blood lipid-lowering effects of an Antrodia cinnamomea mycelia powder complex according to the safety assessment guideline of Health Food announced by Ministry of Health and welfare, Executive Yuan of Taiwan. Methods: A total of 32 hyperlipidemia individuals with TC > 200 mg/dl were randomly divided in- to intervention group (n = 16) and placebo group (n = 16). Dietary intervention was provided for the intervention group for 2 months. Information on dietary intakes, physical examinations and blood samples was collected. Serum lipids were assayed at baseline and endpoint of the study pe- riod. Subjects take two capsules of A. cinnamomea mycelia powder complex or placebo twice a day. The study has 2 weeks run in period, 8 weeks intervention period, and 4 weeks follow-up period.
All subjects measure body weight, body fat, blood pressure and biochemical parameters, including Triglycerides (TG), total cholesterol (TC), low density lipoprotein in cholesterol (LDL-C), high den- sity lipoprotein in cholesterol (HDL-C), blood sugar, kidney and liver function. Results: The results were found after 8 weeks intervention, the plasma total cholesterol and LDL-C were significantly decreased compared with the initial, and there was significantly difference (p < 0.05) compared with the placebo group. LDL-C/HDL-C and Triglyceride level has a decreasing trend. Conclusion: A. cinnamomea mycelia powder complex could decrease blood lipids.
The major pathologic hallmark of the alcoholic liver disease (ALD) is the representation of chronic alcohol-induced hepatocyte lipid accumulation. This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia (ACT) in chronic alcohol-induced liver injury mice, establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks. In long-term alcohol consumption mice, the significantly lost body weight, increased organ indexes, hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration, showing its hepatoprotective property. ACT suppressed the Triglyceride , total cholesterol and low-density lipoprotein levels, and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice.
Combining with the pathological observations, ACT displayed an anti-steatosis effects to restrain the progress of ALD. Based on proteomic analysis and enzyme-linked immunosorbent assay, ACT had been confirmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species. According to further data, ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1α and NF-κB signaling. In summary, ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.
HYPOLIPIDEMIC EFFECTS OF ANTRODIA CINNAMOMEA EXTRACTS IN HIGH-FAT DIET-FED HAMSTERS
Antrodia cinnamomea (AC) is a popular medicinal fungus used for treating hypertension, hepatotoxicity and tumors. This study aimed to examine the hypolipidemic properties of A. cinnamomea extracts (ACE) in high-fat diet-fed hamsters. Results showed that at concentrations 500, 1,000 and 1,500 mg/kg, ACE showed no significant effect on total cholesterol and high-density lipoprotein concentrations, but a trend of decrease in plasma Triglycerides and low-density lipoprotein (LDL) levels was noted, and a significant reduction in LDL was observed at 1,500mg/kg ACE. ACE caused a significant decrease in liver Triglycerides and total cholesterol concentrations. ACE possessed the ability to enhance superoxide dismutase, catalase and glutathione peroxidase production, and reduced the thiobarbituric acid-reactive substances level in hyperlipidemic hamsters. These results conclude that ACE is able to lower the plasma Triglycerides and LDL, liver Triglycerides and total cholesterol concentrations, as well as enhancing the level of antioxidant enzymes.
apigenin 7-O-β-D glucoside
Oral administration of apigenin 7-O-β-D glucosidereverses hyperlipidemia and associated
vascular dysfunction in rats
Apigenin 7‑O‑β‑D‑glucoside is a flavonoid reported as smooth muscle relaxant, anti-inflammatory, and anti-oxidant, suggesting its role in cardiovascular disease. The present study aimed to investigate theeffect of apigenin 7‑O‑β‑D‑glucoside on hyperlipidemia and associated vascular dysfunction in rats. Oral administration of apigenin 7‑O‑β‑D‑glucoside to HFD and tyloxopol-induced hyperlipidemic SD rats for 28 and 10 days that reduced significantly (p < 0.01),
totalcholesterol,LDL, VLDL and Triglycerides , and increased HDL levels and also reduced the total body weight and atherogenic index suggesting its antihyperlipidemiceffect. Thiseffect wasfurther confirmed when the compound also inhibited the key enzyme HMG-CoA reductase in the biosynthesis ofcholesterol.
Apigenin 7‑O‑β‑D‑glucoside is a flavonoid reported as smooth muscle relaxant, anti- inflammatory, and anti-oxidant, suggesting its role in cardiovascular disease. The present study aimed to investigate the effect of apigenin 7‑O‑β‑D‑glucoside on hyperlipidemia and associated vascular dysfunction in rats. Oral administration of apigenin 7‑O‑β‑D‑glucoside to HFD and tyloxopol-induced hyperlipidemic SD rats for 28 and 10 days that reduced significantly (p < 0.01), total cholesterol, LDL, VLDL and Triglycerides , and increased HDL levels and also reduced the total body weight and atherogenic index suggesting its antihyperlipidemic effect.
This effect was further confirmed when the compound also inhibited the key enzyme HMG-CoA reductase in the biosynthesis of cholesterol. The devastating effects on vascular architecture such as change in the aortic intima, media, adventitia and also the endothelium damage, were reversed in apigenin 7‑O‑β‑D‑glucoside 5 mg/kg/day treated group. In the in vitro studies, the compound reversed the endothelial damage demonstrated by significant vasorelaxation in the aortic rings from hyperlipidemic rats treated with apigenin 7‑O‑β‑D‑glucoside 5 mg/kg/day, with EC50 value of 0.02 μg/mL (0.01-0.20) compared to hyperlipidemic HFD rats, similar to atorvastatin. These findings indicate that antihyperlipidemic effect of apigenin 7‑O‑β‑D‑glucoside is mediated through decrease in total cholesterol, LDL, VLDL, Triglyceride level and increase in level of HDL through inhibition of HMG-CoA inhibition and also improved the associated histopathological changes and endothelium dysfunction.
Apocynum venetum
Apocynum leaf extract inhibits the progress of atherosclerosis in rats via the AMPK/mTOR pathway
Apocynum leaf extract is an extract of the dried leaves of Apocynum venetum (a member of the Apocynaceae family) that has many effects on the cardiovascular system. The aim of the present study was to evaluate the protective effects of apocynum leaf extract on the atherosclerosis in rats induced by high-fat diet combined with vitamin D3 intraperitoneal injection. The atherosclerosis in rats were induced with a high-fat diet and an intraperitoneal injection of VD3 once daily for three contiguous days at a total injection dose of 70 U/kg. At the end of the 18th week, serum total cholesterol (TC) and Triglyceride (TG) contents were measured. Hydroxyproline content in the aorta were measured by the alkali hydrolysis method. The hematoxylin-eosin (HE) and immunohistochemical staining were applied to evaluate the morphological changes and the collagen I and α-smooth muscle actin expression. The protein expression and the mRNA level of AMPK and mTOR were detected by western blot analysis and reverse transcript PCR.
Areca catechu L. Extract
Areca extracts have already been found to exhibit a strong inhibitory activity on cholesterol absorption in high-cholesterol-fed rats. Accordingly, this study was performed to determine whether Areca extracts also exert an inhibitory activity on Triglyceride absorption in Triglyceride-fed rats. Male rats were fed a diet containing corn oil (10%, w/w) with or without an Areca nut extract supplement (0.5%, w/w). The supplementation of the Areca extract significantly lowered the absorption of Triglyceride and the plasma lipid concentration. The absorbed Triglyceride that appeared in the blood after an oral dose of [9,10(n)-3H] Triglyceride was significantly lower in the rats supplemented with the Areca nut extract, compared with the control group. The supplementation also significantly lowered the small intestinal pCEase (pancreatic cholesterol esterase) activity by 22.5% compared to the control group.
Aporosa lindleyana
cholesterolloweringeffect OF Aporosa lindleyana IN MALE WISTAR RATS
Aporosa lindleyana is a green leafy vegetable of family Euphorbiaceae grown in tropical countries. In this study theeffect of Aporosa lindleyana on theserumcholesterol level of hypercholestero-laemic rats and normocholesterolaemic Wistar rats fed on acholesterol enricheddiet was investigated. The results indicate that feeding of plant extract for two weeks reduces the total cholesterol in hypercholesterolaemic Wistar rats by 25.2% and normocholesterolaemic rats fed with cholesterol enricheddiet by 37.7%. In addition the test group had significantly lower (p<0.05) total/HDL than the controls indicating that Aporosa lindleyana extract possesses hypochlosterolaemic activity.
Artemisia capillaris Thunb.extract
Antioxidant andlipid-lowering effects of Artemisia capillaris on a Rat Model of Hyperlipidemia
Objectives: This study was designed to evaluatelipid-lowering and antioxidanteffects of Artemisia capillaris (A. capillaris) using a model of hyperlipidemic rats induced by poloxamer-407.
Methods: Rats were previously treated by A. capillaris water extract, and intraperitoneally injected by poloxamer-407 to induce hyperlipidemia. Parameters of serum lipid and oxidative stress biomarkers were determined.
Results:
1. A. capillarisameliorated the elevation ofserum totalcholesterol, Triglyceride, LDL-cholesterol and MDA level.
2. A. capillarisameliorated the reduction ofserum TAC and SOD activities.
3. A. capillarisameliorated the reduction ofserum GSH and GSH-reductase level.
Conclusions: According to these results, A. capillaris can be used to treat hyperlipidemia or as basis for making new drugs for treating hyperlipidemia in the future.
Antioxidant and Lipid-lowering Effects of Artemisia capillaris on a Rat Model of Hyperlipidemia
Hyperlipidemia, also known as hyperlipoproteinemia, refers to the excess status of fatty substances including cholesterol, Triglycerides or lipoproteins in the bloodstream1,2). Hyperlipidemia is an important risk factor in developing heart disease and stroke which are leading causes of death in most developed countries, including Korea3,4). Accordingly, the appropriate control of lipid levels in the bloodstream is a standard strategy to prevent the development of vascular disease5). There are four classes of lipid lowering drugs: 3-hydroxy-3-methylglutaryl coenzyme A(HMG- CoA) reductase inhibitors commonly referred to as statins, bile acid sequestrants, nicotinic acid, and fibric acids6,7). These hypolipidemic agents lower lipid levels somewhat, but have a limitation due to lack of final clinical outcome in prevention of heart disease and stroke, and often adverse effects such as hepatotoxicity, myopathy or noncardiovascular death8,9)
Artemisinin (Artemisia annua L.)
Objectives: Artemisinin and its derivatives extracted from Artemisia annua, a Chinese herbal medicine, have variable biological effects due to structural differences. Up to date, the anti-obesity effect of dihydroartemisinin (DHA), a derivative of artemisinin, is unknown. The purpose of this study was to investigate the anti-adipogenic and lipolytic effects of DHA on 3T3-L1 preadipocytes.
Methods: Oil Red O staining and AdipoRed assay were used to measure lipid accumulation and Triglyceride (TG) content in 3T3-L1 cells, respectively. Cell count analysis was used to determine the cytotoxicity of 3T3-L1 cells. Western blot and real-time reverse transcription polymerase chain reaction analyses were used to analyze the expression of protein and mRNA in 3T3-L1 cells, respectively.
Results: DHA at 5 μM markedly inhibited lipid accumulation and reduced TG content in differentiating 3T3-L1 cells with no cytotoxicity. Furthermore, DHA at 5 μM inhibited the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A as well as the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells. Moreover, while DHA at 5 μM had no effect on the mRNA expression of adiponectin, it strongly suppressed that of leptin in differentiating 3T3-L1 cells. However, DHA at 5 μM had no lipolytic effect on differentiated 3T3-L1 cells, as assessed by no enhancement of glycerol release.
Conclusions: These results demonstrate that DHA at 5 μM has a strong anti-adipogenic effect on differentiating 3T3-L1 cells through the reduced expression and phosphorylation of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3.
Artemisia annua extract ameliorates high-fat diet-induced fatty liver by activating AMPK
Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Recently, natural compounds that may be beneficial for improving NAFLD have received increasing attention. Artemisia annua L. is the source of antimalarial phytomolecule, artemisinin, which has been reported to prevent obesity. However, the effect of A. annua extract on hepatic lipid metabolism remains unclear. This study was performed to determine the protective effect of Artemisia annua extract (AAE) on high-fat diet (HFD)-induced hepatic lipid accumulation, and elucidate the molecular mechanisms behind its effects in vivo and in vitro. We found that HFD-fed mice with AAE administration (50 mg/kg/day) for 8 weeks dramatically reduced hepatic lipid accumulation compared to the control mice taken with HFD alone.
The body and liver weights of AAE group were significantly lower than those of HFD group, and oral administration of AAE remarkably suppressed the serum levels of Triglyceride (TG), total cholesterol (TC), fasting glucose, alanine transaminase (ALT) and aspartate transaminase (AST) in HFD-fed mice. AAE significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in the liver of HFD-fed mice and HepG2 hepatocytes. Moreover, AAE downregulated the hepatic expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in HFD-fed mice and high glucose-treated HepG2 cells. In addition, the inhibitory effects of AAE on the overexpression of SREBP-1c and FAS were attenuated by compound C, which is the specific AMPK inhibitor, in high glucose-treated HepG2 cells. These results indicated that AAE may represent a promising approach for the prevention and treatment of obesity-related NAFLD via the activation of AMPK and the regulation of AMPK-dependent lipogenic genes.
Artichoke Extract cynarin
General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or Triglyceride levels.
Artocarpus ovatus Blanco
Artocarpus ovatus Blanco is a plant species of the Philippines belonging to the family Moraceae. This study evaluated thecholesterol-lowering activity of the A. ovatus ethanolic leaf extract in Sprague Dawley rats and its acute oral toxicity. It was found to be safe and non-toxic up to 2000 mg/kg BW of test animals based on the guidelines of OECD 425 main test. Post toxicity test gross necropsy results are unremarkable. In thecholesterollowering bioassay, the ethanolic extract treated rats at doses of 200, 400 and 600 mg/kg showed time dependent reduction ofserum levels of totalcholesterol, Triglycerides and low density lipoproteins with p-values less than 0.05.high density lipoproteins concentrationimproved,high catalase enzyme levels and unremarkable degree oflipid peroxidation were measured and observed after 14 days of oral administration of the extract.
In vivo cholesterol-lowering bioassay results Mean serum total cholesterol, Triglycerides , HDL and LDL values were significant to all the experimental groups (p values < 0.05). After the 14-day treatment period, groups III, IV, V and VI (200 to 600 mg/kg extract treated groups and positive control group) have decreased total cholesterol, Triglycerides and LDL levels. However post hoc analysis showed that groups IV and V (400 and 600 mg/kg extract treated groups) have no significant difference in reducing total cholesterol. The treatment groups (200 to 600 mg/kg extract treated groups) do not statistically differ in improving mean HDL serum levels with the positive control group (p values > 0.05). This demonstrates that the ethanolic extract exhibited cholesterol-lowering effect comparable to the positive control on animal rat models.
Presence of excessive levels of cholesterol in the blood indicates a strong risk factor for cardiovascular diseases. Maintenance of low levels of cholesterol in the blood is clinically and importantly considered through the use of pharmaceutical agents such as the statin drugs (HMG-CoA reductase inhibitors) and the fibrates [11]. Medicinal plants can also be utilized as alternative sources of these established remedies but most of them must be clinically studied further. The results of this study suggest that the A. ovatus ethanolic leaf extract have a medicinal potential specifically in lowering cholesterol levels in rat animal models. Figures 1 to 4 present the mean total cholesterol, Triglycerides , HDL and LDL levels of the experimental groups.
Astragalus membranaceus
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protectiveeffects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments anddiet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of totalcholesterol andLDLcholesterol (P < 0.05 to 0.01), increased HDLcholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and thiseffect increased withhigher TFA concentration. In in vivo experiments, TFAeffectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve theAtherosclerosis profile.
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol ( to 0.01), increased HDL cholesterol levels ( ), and reduced the aortic fatty streak area by 43.6 to 63.6% ( ). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile.
Astragalus membranaceus is a Traditional Chinese Medicine (TCM) belonging to the Leguminosae family. It has been used as antidiabetic, cardioprotective, and hepatoprotective in the TCM clinic. From the stems of A. membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, 14 oleanane type saponins (1–14) including eight new ones, astroolesaponins A (1), B (2), C1 (3), C2 (4), D (5), E1 (6), E2 (7), and F (8) were obtained, and their structures were elucidated by chemical and spectroscopic methods. Compounds 1–5, 7, 8, 11, and 13 showed decreased effects on Triglyceride levels in sodium oleate induced HepG2 cells.
Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer’s disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic Triglyceride . Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.
Astragalus mongholicus
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protectiveeffects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments anddiet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of totalcholesterol andLDLcholesterol (P < 0.05 to 0.01), increased HDLcholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and thiseffect increased withhigher TFA concentration. In in vivo experiments, TFAeffectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve theAtherosclerosis profile.
Astragalus mongholicus is a Chinese traditional medicine. In this study, we sought to explore potential benefits in cardiovascular disorders associated with excess cholesterol and hyperlipidemia. We have investigated the effects of A. mongholicus extract as a dietary supplement on hyperlipidemia and oxidative stress in rats maintained on a high- cholesterol diet. Diets were supplemented with A. mongholicus extract at 0.4 and 0.8% for five weeks, while control animals received no supplement. A. mongholicus extract administration to hyperlipidemic rats resulted in a significant decline in serum levels of total cholesterol, Triglycerides and low density lipoprotein-cholesterol, with an increase in serum high-density lipoprotein-cholesterol levels. Furthermore, A. mongholicus extract improved serum and heart antioxidant status as assessed by superoxide dismutase and glutathione peroxidase activities and reduced levels of lipid peroxidation. These results suggest that A. mongholicus extract consumption can improve lipid profiles, inhibit peroxidation, and increase the activity of antioxidant enzymes, and is thereby likely to reduce the risk of coronary heart disease associated with hyperlipidemia and oxidative stress.
Avena sativa extract β- glucan
There was a significant reduction in blood glucose, serum liver enzymes, Triglycerides, and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.
Basella alba
Hypercholesterolemia is the major risk factor that leads toAtherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse healtheffects, especially liver and muscle toxicity. This study was designed to investigate thehypocholesterolemic andAntiatheroscleroticeffects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varyingdiets: normaldiet, 2%highcholesteroldiet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of totalcholesterol,LDL, and Triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia andAtherosclerosis.
Twenty New Zealand white rabbits were divided into 5 groups and fed with normal diet (G1), 2% high cholesterol diet (HCD) (G2), 2% HCD + 10 mg/kg simvastatin
(G3), 2% HCD + 100 mg/kg B. alba extract (G4) and 2% HCD + 200 mg/kg B. alba extract (G5), respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol (TC), low density lipoptotein (LDL) and Triglyceride (TG). The significant increase in high density lipoprotein (HDL) and antioxidant enzymes; superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels observed in treatment with B. alba extract (G4 and G5) compared to the treatment with simvastatin (G3). The elevated levels of liver enzymes; alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and muscle enzyme; creatine kinase (CK) were noted in G2 and G3 indicate liver and muscle injuries. Treatment with simvastatin (G3) and B. alba extract (G4 and G5) significantly suppressed the aortic plaque formation. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.
The enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of the mevalonate pathway that produces cholesterol. Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia. Due to the side effects of statins, natural HMG-CoA reductase inhibitors of plant origin are needed. In this study, 25 medicinal plant methanol extracts were screened for anti-HMG-CoA reductase activity. Basella alba leaf extract showed the highest inhibitory effect at about 74%. Thus, B. alba was examined in order to investigate its phytochemical components. Gas chromatography with tandem mass spectrometry and reversed phase high-performance liquid chromatography analysis revealed the presence of phenol 2,6-bis(1,1-dimethylethyl), 1-heptatriacotanol, oleic acid, eicosyl ester, naringin, apigenin, luteolin, ascorbic acid, and α-tocopherol, which have been reported to possess antihypercholesterolemic effects. Further investigation of in vivo models should be performed in order to confirm its potential as an alternative treatment for hypercholesterolemia and related cardiovascular diseases.
Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and Triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.
Berberine
Regulation ofPCSK9 by nutraceuticals
PCSK9, a criticalInhibitor ofLDLR, is up-regulated by both HNF1α and SREBP-2 transcription factors. Besides
PCSK9, SREBP-2 up-regulatesLDLR gene. Nutraceuticals, including curcumin and berberine, can decrease plasma
LDL-C levels through elevation of the hepaticLDLR via inhibiting HNF1α which is a specific transcription factor
forPCSK9 gene. Statins increase the expression of bothPCSK9 andLDLR through the activation of SREBP-2,
resulting inPCSK9-mediated attenuation of theireffects.
Naturally OccurringPCSK9Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
The aim of this study was to investigate the role of the mevalonate pathway in the cytostatic/cytotoxiceffects of berberine, a natural plant alkaloid that reducescholesterol concentration. Berberine as well as lovastatin, anInhibitor of the mevalonate pathway, exerted dose-dependent cytostatic/cytotoxiceffects against human breast cancer cells (MDA-MB231). Although the mevalonate pathway metabolites (mevalonic acid, farnesyl pyrophosphate, geranylgeranyl pyrophosphate)effectivelyreversed cytostatic/cytotoxiceffects of lovastatin against MDA-MB231 cells, they were noteffective in influencing the cytostatic/cytotoxiceffects of berberine. The cytostatic/cytotoxiceffects of berberine do not seem to result from inhibition of the mevalonate pathway.
Ethnopharmacological relevance
Rhizoma coptidis (Huanglian in Chinese) is commonly used in Chinese folk medicine to treat diarrhea, diabetes, hypertension, hyperlipidemia and tumors. This herb has increasingly gained attention because of its use as a hypolipidemic herb. Berberine (BBR) is the most important constituent of R. coptidis that contribute to the pharmacological efficacy of the herb.
Aim of the study
Pharmacokinetic studies have indicated that BBR has poor oral bioavailability. Interestingly, several reports show that absorbed BBR is extensively metabolized in rats and humans. We speculate that the BBR metabolites might be responsible for the pharmacological effects. The aim of this study is to examine BBR metabolites for their Triglyceride (TG)-lowering activities and the molecular mechanism to clarify BBR genuine effective forms in vivo.
Materials and methods
Four BBR metabolites were examined their TG-lowering effects with a commercial Triglyceride assay kit. Real-time PCR and Western blotting were used to confirm genes and proteins of interest, respectively.
Results
Among those BBR metabolites, M2 exhibited the more potential effects on TG-lowering and AMP-activated protein kinase (AMPK) activation in Hep G2 cells as compared with BBR. Moreover, BBR and M2 inhibited gene expressions of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), but motivated gene expression of medium chain acyl-CoA dehydrogenase (mCAD) significantly.
Conclusions
The results suggested that the TG-lowering effects of BBR and M2 might be partially mediated by the up-regulation of lipolysis gene expressions and down-regulation of lipogenesis gene expressions through activation of the AMPK signaling pathway. BBR and its metabolites might be in vivo active forms of oral doses of BBR, and M2 might be a promising drug candidate against hyperlipidemia.
Lipid-lowering effect of berberine in human subjects and rats
Due to serious adverse effects and the limited effectiveness of currently available pharmacological therapies for obesity, many research efforts have focused on the development of drugs from natural products. Our previous studies demonstrated that berberine, an alkaloid originally isolated from traditional Chinese herbs, prevented fat accumulation in vitro and in vivo. In this pilot study, obese human subjects (Caucasian) were given 500 mg berberine orally three times a day for twelve weeks. The efficacy and safety of berberine treatment was determined by measurements of body weight, comprehensive metabolic panel, blood lipid and hormone levels, expression levels of inflammatory factors, complete blood count, and electrocardiograph. A Sprague-Dawley rat experiment was also performed to identify the anti-obesity effects of berberine treatment. The results demonstrate that berberine treatment produced a mild weight loss (average 5 lb/subject) in obese human subjects. But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of Triglyceride and 12.2% decrease of cholesterol levels) in human subjects. The lipid-lowering effect of berberine treatment has also been replicated in the rat experiment (34.7% decrease of Triglyceride and 9% decrease of cholesterol level). Cortisol, calcitriol, ACTH, TSH, FT4, and SHBG levels were not significantly changed following 12 weeks of berberine treatment. However, there was interestingly, an increase in calcitriol levels seen in all human subjects following berberine treatment (mean 59.5% increase, p = 0.11). Blood inflammatory factors (CRP, IL-6, TNFα, COX-2) and erythrocyte sedimentation rate (ESR) were not significantly affected by treatment with berberine. Tests of hematological, cardiovascular, liver, and kidney function following berberine treatment showed no detrimental side effects to this natural compound. Collectively, this study demonstrates that berberine is a potent lipid-lowering compound with a moderate weight loss effect, and may have a possible potential role in osteoporosis treatment/prevention.
Effects of berberine on lipid profile in subjects with low cardiovascular risk
Objective: To evaluate the efficacy as antihypercholesterolemic agent of berberine in patients with low cardiovascular risk.
Research design and methods: 144 Caucasian subjects were enrolled. After a 6-month run-in period following diet and practicing physical activity, patients were randomized to take placebo or berberine 500 mg twice a day, for 3 months, in a double-blind, placebo-controlled design. Berberine and placebo were then interrupted for 2 months (washout period), and all patients continued with only diet and physical activity. At the end of the washout period, patients restarted berberine or placebo twice a day for further 3 months. Anthropometric and metabolic parameters were assessed during the run-in period, at randomization, before and after the washout period.
Results: A decrease of body weight and BMI was observed after the run-in period. Berberine reduced total cholesterol, Triglycerides and LDL cholesterol and increased HDL cholesterol after 3 months from randomization and compared with placebo. After the washout period, lipid profile worsened; afterward, when berberine was reintroduced, lipid profile improved again both compared with the washout period, and with placebo.
Conclusions: Berberine is effective and safe to mildly improve lipid profile in subjects with low risk for cardiovascular disease.
Effect of Berberine Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion
Background: The aim of this study was to evaluate the effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion.
Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with a diagnosis of metabolic syndrome. Glucose and insulin levels after a dextrose load were measured. Triglycerides and high-density lipoprotein cholesterol concentrations at baseline were also measured. Twelve patients received berberine hydrochloride (500 mg) three times daily before meals for 3 months. The remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were assessed.
Results: After berberine administration, patients had a remission of 36% (P=0.037) in the presence of metabolic syndrome and a significant decrease in waist circumference in females (106±4 vs. 103±3 cm, P<0.05), systolic blood pressure (SBP) (123±7 vs. 115±9 mmHg, P<0.01), Triglycerides (2.4±0.7 vs. 1.4±0.5 mmol/L, P<0.01), area under the curve (AUC) of glucose (1182.1±253.6 vs. 1069.5±172.4 mmol/l, P<0.05), AUC of insulin (92,056±72,148 vs. 67,407±46,441 pmol/L, P<0.01), and insulinogenic index (0.78±0.69 vs. 0.62±0.46, P<0.05), as well as an increase in the Matsuda index (2.1±1.0 vs. 3.1±1.6, P<0.01).
Conclusions: Administration of berberine leads to remission of metabolic syndrome and decreases in waist circumference, SBP, Triglycerides , and total insulin secretion, with an increase in insulin sensitivity.
Efficacy of berberine in patients with type 2 diabetes mellitus
Berberine has been shown to regulate glucose and lipid metabolism in vitro and in vivo. This pilot study was to determine the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus patients. In study A, 36 adults with newly diagnosed type 2 diabetes mellitus were randomly assigned to treatment with berberine or metformin (0.5 g 3 times a day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (from 9.5% ± 0.5% to 7.5% ± 0.4%, P < .01), fasting blood glucose (from 10.6 ± 0.9 mmol/L to 6.9 ± 0.5 mmol/L, P < .01), postprandial blood glucose (from 19.8 ± 1.7 to 11.1 ± 0.9 mmol/L, P < .01), and plasma Triglycerides (from 1.13 ± 0.13 to 0.89 ± 0.03 mmol/L, P < .05) were observed in the berberine group. In study B, 48 adults with poorly controlled type 2 diabetes mellitus were treated supplemented with berberine in a 3-month trial. Berberine acted by lowering fasting blood glucose and postprandial blood glucose from 1 week to the end of the trial. Hemoglobin A1c decreased from 8.1% ± 0.2% to 7.3% ± 0.3% (P < .001). Fasting plasma insulin and homeostasis model assessment of insulin resistance index were reduced by 28.1% and 44.7% (P < .001), respectively. Total cholesterol and low-density lipoprotein cholesterol were decreased significantly as well. During the trial, 20 (34.5%) patients experienced transient gastrointestinal adverse effects. Functional liver or kidney damages were not observed for all patients. In conclusion, this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism.
TRIB1 is a GWAS locus associated with plasma cholesterol and Triglycerides (TG) levels. In mice, liver-specific overexpression of TRIB1 lowers plasma lipid levels. Berberine (BBR) is a natural lipid lowering drug that reduces plasma LDL-cholesterol (LDL-C), total cholesterol (TC) and TG in hyperlipidemic patients and in mice by mechanisms involving upregulation of hepatic LDL receptor (LDLR). Here, we demonstrated that BBR treatment reduced plasma LDL-C, TC and TG in LDLR wildtype (WT) mice fed a high fat and high cholesterol diet and it only lowered TG in LDLR WT mice fed a normal chow diet. In hypercholesterolemic LDLR deficient mice (Ldlr−/−), BBR treatment reduced plasma TG levels by 51% compared to the vehicle control without affecting plasma cholesterol levels. Hepatic gene expression analysis revealed that Trib1 mRNA levels were significantly elevated by BBR treatment in all three mouse models and increases of Trib1 mRNA expression were associated with reduced expression of lipogenic genes including Cebpa, Acc1 and Scd1. In vitro studies further demonstrate that BBR induces TRIB1 mRNA expression by a transcriptional mechanism via ERK signaling pathway. These new findings warrant future in vivo studies to determine the causal role of Trib1 in BBR-mediated TG lowering independent of LDLR regulation.
Berberis lycium
Role of Berberis lycium inreducingserumcholesterol in Broilers
This study was planned to investigate the role of Berberis lycium inreducingserumcholesterol in broilers. Six experimental rations designated as A, B, C, D, E and F having 0, 0.5, 1.0, 1.5, 2.0 and 2.5% Berberis lycium were fed to 240 broiler chicks, randomly distributed into 24 replicates, so as to have 4 replicates per group and 10 chicks per replicate. The experiment lasted for 35 days. Averageserum totalcholesterol, Triglyceride ,high density lipoprotein (HDL) and low density lipoprotein (LDL) were used as criteria of response. Average totalserumcholesterol per chick was 129.33, 120.50, 116.50, 113.00, 101.67 and 114.00 mg/dl for group A, B, C, D, E and F respectively. Totalserumcholesterol showed decreasing trend with the increasing level of Berberis lycium unto 2% (p<0.05). Meanserum Triglyceride level per chick was 60.00, 58.17, 58.00, 55.33, 50.17 and 48.50 mg/dl for group A, B, C, D, E and F respectively. Meanserum Triglyceride showed decreasing trend with the increasing level of Berberis lycium (p<0.05).serum Triglyceride was significantly lower in group F than other groups. Mean HDL per chick for the six experimental groups A, B, C, D, E and F was 52.08, 53.42, 60.42, 62.25, 62.92 and 54.50 mg/dl respectively. HDL showed increasing trend with the increase in the level of Berberis lycium unto 2%. The averageserumLDL per chick was 65.25, 55.45, 44.48, 39.68, 28.72 and 49.80 mg/dl for group A, B, C, D, E and F respectively.LDL also showed decreasing trend with the increase in the level of Berberis lycium unto 2% (p<0.05). It was concluded that Berberis lycium added to feed at the rate of 2.0% can be used in broiler feed forreducingserum totalcholesterol, Triglyceride andLDL and increasing HDL.
Role of Berberis lycium in reducing serum cholesterol in broilers
This study was planned to investigate the role of Berberis lycium in reducing serum cholesterol in broilers. Six experimental rations designated as A, B, C, D, E and F having 0, 0.5, 1.0, 1.5, 2.0 and 2.5% Berberis lycium were fed to 240 broiler chicks, randomly distributed into 24 replicates, so as to have 4 replicates per group and 10 chicks per replicate. The experiment lasted for 35 days. Average serum total cholesterol, Triglyceride , high density lipoprotein (HDL) and low density lipoprotein (LDL) were used as criteria of response. Average total serum cholesterol per chick was 129.33, 120.50, 116.50, 113.00, 101.67 and 114.00 mg/dl for group A, B, C, D, E and F respectively. Total serum cholesterol showed decreasing trend with the increasing level of Berberis lycium unto 2% (p<0.05). Mean serum Triglyceride level per chick was 60.00, 58.17, 58.00, 55.33, 50.17 and 48.50 mg/dl for group A, B, C, D, E and F respectively. Mean serum Triglyceride showed decreasing trend with the increasing level of Berberis lycium (p<0.05). Serum Triglyceride was significantly lower in group F than other groups. Mean HDL per chick for the six experimental groups A, B, C, D, E and F was 52.08, 53.42, 60.42, 62.25, 62.92 and 54.50 mg/dl respectively. HDL showed increasing trend with the increase in the level of Berberis lycium unto 2%. The average serum LDL per chick was 65.25, 55.45, 44.48, 39.68, 28.72 and 49.80 mg/dl for group A, B, C, D, E and F respectively. LDL also showed decreasing trend with the increase in the level of Berberis lycium unto 2% (p<0.05). It was concluded that Berberis lycium added to feed at the rate of 2.0% can be used in broiler feed for reducing serum total cholesterol, Triglyceride and LDL and increasing HDL.
Effect of Berberis lycium Royle on Lipid Profile in Alloxan Induced Diabetic Rabbits
Berberis lycium Royle (B.l.R) commonly known as Ishkeen (Kashmal and Darbald) is widely used in folk medicines for the treatment of Diabetes mellitus. Experimental diabetes use to alter the lipid profile. The aim of the present study was to evaluate the effects of Berberis lycium root bark on various lipid profiles in alloxan induced diabetic rabbits. Diabetes was induced by single intravenous injection of Alloxan (150 mg/kg).Oral administration of 250mg/kg and 500mg/kg crude powder of Berberis lycium root for four weeks resulted in significant reduction in total cholesterol, Triglyceride and low density lipids (LDLs) levels. Berberis lycium treatment increased the levels of high density lipids (HDLs). Furthermore same doses stabilized the weight of diabetic rabbits. Thus our investigation clearly shows that crude powder of Berberis lycium Royle has antihyperlipidemic effect.
Hyperlipidemia is a condition in which blood is overloaded with lipids. This condition is challenging for living beings. There are many ways to solve this problem but herbal medicines
take on paramount importance in this regard. The purpose of the current research was to inspect the effects of an aqueous extract of Berberis lycium Royle root bark on lipid profiles of Swiss albino mice in which diabetic phenotype was induced by alloxan. A single injection of Alloxan (150 mg/kg) was applied intravenously to induce diabetic phenotype. Alloxan induction raised the overall level of Triglycerides , low density- lipids (LDLs), and cholesterol and reduced the level of high density lipids (HDLs). Oral administration of 200 mg/kg aqueous extract of B. lycium Royle root bark for 28 days rescued all these changes. This study shows that the root bark extract of B. lycium Royle has antihyperlipidemic properties.
Berberine has been shown to have hypoglycaemic activity in several in vitro and in vivo models, although the mechanism of action is not fully known. Berberis lyceum Royle root produces high concentrations of berberine, and in traditional medicine, the whole extract of this plant is used widely to treat diabetes. The antidiabetic activity of the ethanol root extract of Berberis lyceum was compared with pure berberine in normal and alloxan-diabetic rats using similar doses of each. The concentration of berberine in the extract was determined to be 80% dry weight with only trace amounts of other alkaloids present. The purpose of the study was to investigate the effects of berberine and a whole extract of Berberis lyceum on blood glucose and other parameters associated with diabetes, to compare the effects of the crude extract with those of pure berberine and thus validate its use as a therapeutic agent, and finally to identify any contribution of the other components of the extract to these effects.
Oral administration of 50 mg/kg of Berberis extract and berberine to normal and experimental diabetic rats produced a significant (p < 0.05) reduction in blood glucose levels from days 3–7 days of treatment. Significant effects were also observed on the glucose tolerance, glycosylated haemoglobin, serum lipid profiles and body weight of experimental animals. Berberis extract and berberine demonstrated similar effects on all parameters measured, and although the extract was comparable in efficacy to berberine, it did not produce any effects additional to those shown by pure berberine. The results support the use of the extract in traditional medicine, and demonstrate that apart from being a highly cost-effective means of treating with berberine, the total extract does not appear to confer any additional benefits or disadvantages compared with the pure compound.
Chemistry and Biological Activities of Berberis lycium Royle
Berberis lycium Royle belonging to family Berberidaceae is a high-value medicinal plant with a known history of uses in folk medicine. It is used traditionally for curing a broad range of human illnesses and diseases in the Indian Himalayan region of Pakistan, India, and Bangladesh. Its ethnomedicinal uses include its use for treatment of jaundice, diabetes, eye infections, fractured bones, internal wounds, diarrhea, rheumatism, stomachache, and its use as a general body tonic. Although its every part has some medicinal properties, the most commonly used parts are roots and stem-bark. Its biologically active phytochemicals are alkaloids with berberine as the major one. An analysis of literature shows that its main biological activities are mainly attributed to berberine.Available literature shows that the plant has a wide range of biological activities including antihyperglycemic, antihyperlipidemic, anticancer and antitumor, wound and bone healing, antimicrobial, anticoccidial, antioxidant, hypotensive, immunity enhancing, antiurolithic, anthelmintic and hepatoprotective. Its wide use in folk medicine has prompted research in its phytochemical constituents and biological activities over the last four decades. Research in these lines is attesting its ethnomedicinal uses.This review paper is aimed to explore the chemistry and biological activities of this gifted medicinal plant.
Bergamot (Citrus bergamia)
The bergamot is a citrus fruit native to southern Italy with traditional uses that include improving immune response and cardiovascular function. There are a variety of phytochemicals that have been found in the bergamot including brutieridin and melitidin as well as other flavonoids, flavones O-glucosides and C-glucosides. Multiple clinical trials have provided evidence that different forms of orally administered bergamot can reduce totalcholesterol and low-density lipoproteincholesterol. In vitro mechanistic studies have provided evidence that polyphenols from the bergamot can alter the function of AMPK and pancreaticcholesterol ester hydrolase (pCEH). The use of bergamot in multiple clinical trials has consistently shown that it is well tolerated in studies ranging from 30 days to 12 weeks. This mini-review reports on the clinical studies performed with different forms of bergamot along with theireffectiveness inreducing totalcholesterol andLDLcholesterol in patients with hypercholesterolemia.
Backgrounds
Recent experiments suggest that Citrus bergamia extracts could benefit people with dyslipidemia and obesity but this needs to be further validated.
Methods
A total of 98 people age-matched older adults (65 years) with elevated blood lipids were enrolled to receive 12-week supplementation of a Citrus bergamia extracts-based formulation (CitriCholess)(n = 48) and placebo (n = 50).
Results
No group differences were found in baseline bodyweight, body mass index (BMI), blood cholesterol (TC), Triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and glucose levels. CitriCholess supplementation resulted in lower levels than placebo in TG (1.83 ± 0.92 vs. 1.95 ± 1.34 mmol/L, P = 0.612), TC (5.14 ± 0.98 vs. 5.44 ± 0.77 mmol/L, P = 0.097), and LDL-C (3.13 ± 0.74 vs. 3.43 ± 0.62 mmol/L, P = 0.032). Compared to placebo, CitriCholess also resulted in greater reductions in body weight (−0.604 ± 0.939 vs. 0.06 ± 0.74 kg, P < 0.01), waist circumferences (−0.60 ± 1.349 cm vs. -0.16 ± 1.503 cm, P < 0.01) and BMI (−0.207 ± 0.357 vs. 0.025 ± 0.274, P < 0.01). Additionally, females had a significantly higher level of HDL-C than males. TC was significantly correlated with LDL-C, and to a less degree, with TG. TG was inversely correlated with HDL-C. Body weight and waist circumference were negatively correlated with HDL-C and positively correlated with glucose.
Conclusion
12-week supplementation of CitriCholess could benefit lipid metabolism and weight management in old adults with dyslipidemia.
The aim of this research was to assess the impact of a well-characterized extract from Citrus bergamia juice on adipogenesis and/or lipolysis using mesenchymal stem cells from human adipose tissue as a cell model. To evaluate the effects on adipogenesis, some cell cultures were treated with adipogenic medium plus 10 or 100 μg/mL of extract. To determine the properties on lipolysis, additional mesenchymal stem cells were cultured with adipogenic medium for 14 days and after this time added with Citrus bergamia for further 14 days. To verify adipogenic differentiation, oil red O staining at 7, 14, 21, and 28 days was performed. Moreover, the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), adipocytes fatty acid-binding protein (A-FABP), adipose Triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), monoglyceride lipase (MGL), 5′-adenosine monophosphate-activated protein kinase (AMPK)α1/2, and pAMPKα1/2 was evaluated by Western blot analysis and the release of glycerol by colorimetric assay. Citrus bergamia extract suppressed the accumulation of intracellular lipids in mesenchymal stem cells during adipogenic differentiation and promoted lipolysis by repressing the expression of adipogenic genes and activating lipolytic genes. Citrus bergamia extract could be a useful natural product for improving adipose mobilization in obesity-related disorders.
The results of five different clinical trials (Table 1) using bergamot in various forms suggest the polyphenol fraction can lower LDL-C and total cholesterol. Several studies suggested that bergamot polyphenols can reduce Triglycerides and increase HDL-C, however, the results were not consistent across all studies. One possible explanation for this variability (i.e. TG and HDL-C) is that bergamot preparation, extraction, and standardization varied in several studies. Consistently in all of the clinical trials bergamot appeared to be well tolerated with studies ranging from 30 days to 6 months. There are several weaknesses in the design of several of the clinical trials that used an open label design (Table 1). However, it should be noted that each patient can serve as their own control since cholesterol was quantified prior to bergamot and at the completion of the study. Three of the studies suggested an increase in HDL by up to 4 mg/dl (Table 1). This is significant because HDL is often difficult to increase apart from lifestyle changes. Regarding the mechanism of action there are several possible mechanisms that may be responsible for improving cholesterol lab values including activation of AMPK and inhibition of pancreatic cholesterol ester hydrolase (pCEH). As of now the suggestions that bergamot inhibits HMG-CoA reductase appear to be largely based on molecular modeling and will require further studies to confirm this proposed mechanism of action. Taken together, these early clinical trials along with the mechanistic studies that have been performed suggest that bergamot can reduce total cholesterol and LDL-C through mechanisms that are distinct from current pharmaceutical approaches.
BACKGROUND:
The role of lipid-lowering and hypoglycemic nutraceuticals in cardiovascular disease prevention is the focus in recent years. The most studied compounds and plants are sterols, soy, red fermented rice, policosanols, artichoke, berberine. Epidemiological and experimental evidences suggest that dietary polyphenols, especially flavonoids, might play a role in preventing atherosclerosis, owing to their pleiotropic metabolic, anti-inflammatory and antioxidant effects. Recent studies have shown that bergamot juice and albedo (Citrus Bergamia Risso et Poiteau), an endemic plant growing in a limited part of the Ionian coast of Calabria (Italy) has a unique content of flavonoids and glycosides, such as neoeriocytrine, neoesperidine, naringenine, routine, neodesmine, polyphenol and poncirine.
OBJECTIVE:
The aim of this study was to investigate the effects of a phytocomplex from bergamot fruit (EP3116520A1) as dietary supplement to a Mediterranean diet on body weight, body mass index (BMI), waist circumference, plasmatic lipid fractions, glucose and C – reactive protein (CRP) in subjects with the metabolic syndrome (MetS; according to NCEP-ATP III criteria) without pharmacological treatment, exept for basic treatment.
METHODS:
80 overweight adults (54% females, 46% males) with the diagnosis of Metabolic Syndrome (MetS), aged 45 ± 5 years, were enrolled and randomized to 2 groups: group A) followed a personalized low calorie Mediterranean diet (control group) and group B) enriched the same diet therapy with 1 tablet of a phytocomplex from bergamot fruit per day for 6 months (intervention group).
RESULTS:
After 6 months patients in the intervention group showed a significant reduction of total cholesterol (–15% ), LDL-Cholesterol (–22% ), Triglycerides (–23% ), blood glucose (–15% ), CRP (–40% ) and a significant increase in the HDL-Cholesterol (+ 14% ) levels compared to the control group (diet alone) where the changes were not significant, with not much significance in reduced body weight.
CONCLUSION:
Our findings suggest that bergamot supplementation improves significantly all aspects of metabolic profile in patients with MetS and is superior to diet alone.
Elevated serum cholesterol, Triglycerides and LDL levels are often associated with an increased incidence of atherosclerosis and coronary artery disease. The most effective therapeutic strategy against these diseases is based on statins administration, nevertheless some patients, especially those with metabolic syndrome fail to achieve their recommended LDL targets with statin therapy, moreover, it may induce many serious side effects. Several scientific studies have highlighted a strong correlation between diets rich in flavonoids and cardiovascular risk reduction. In particular, Citrus bergamia Risso, also known as bergamot, has shown a significant degree of hypocholesterolemic and antioxidant/radical scavenging activities. In addition, this fruit has attracted considerable attention due to its peculiar flavonoid composition, since it contains some flavanones that can act as natural statins. Hence, the study of bergamot flavonoids as metabolic regulators offers a great opportunity for screening and discovery of new therapeutic agents. Cholesterol metabolism, flavonoid composition and potential therapeutic use of C. bergamia Risso will be discussed in the following review.
black Cumin seeds (Nigella sativa L.)
Use of black cumin in layerdiet ascholesterollowering agents in egg yolk
This study was conducted to investigate theeffects of different levels of black cumin seeds (Nigella
sativa L.) on egg production andcholesterol concentration in egg yolk of laying hens. A total of 60
commercial layer strain day old layer chicks were collected and divided into three groups treated with
1.0%, 1.5% and 2.0% black cumin inclusion. The concentrations of totallipids, totalcholesterol,
phospholipids and triacylglycerols inserum and egg yolk were measured. Feeding of thediets with
1%, 1.5% and 2% black cumin seeds during the laying period found egg yolkcholesterol by 11.12,
9.88 and 9.83 mg/g respectively. The results found that feed efficiency ratio, egg production, body
weight, feed intake and egg weight were nonsignificant between the treatments. However, egg yolk
cholesterol concentration was found that 1.5% and 2.0% black cumin indiet were reducedcholesterol
concentration insignificance (P<0.05). So, dried black cumin supplementation indiets had no any
adverseeffect on egg production and egg weight. Furthermore, egg yolkcholesterol concentrations
were decreased. Hence, it is concluded that black cumin (Nigella sativa L.) seeds and/or the active
principle are of interest as potential egg-yolkcholesterol-lowering agents.
The effects of Nigella sativa (NS) on plasma lipid concentrations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (up to August 2015) to identify RCTs investigating the impact of NS on total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and Triglycerides concentrations. A random-effects model and the generic inverse variance weighting method were used for quantitative data synthesis. Meta-regression, sensitivity analysis, and publication bias assessments were performed using standard methods. A total of 17 RCTs examining the effects of NS on plasma lipid concentrations were included. Meta-analysis suggested a significant association between NS supplementation and a reduction in total cholesterol (weighed-mean-difference [WMD]: -15.65mg/dL, 95% CI: -24.67, -6.63, p=0.001), LDL-C (WMD: -14.10mg/dL, 95% CI: -19.32, -8.88, p<0.001), and Triglyceride levels (WMD: -20.64mg/dL, 95% CI: -30.29, -11.00, p<0.001). No significant effect on HDL-C concentrations (WMD: 0.28mg/dL, 95% CI: -1.96, 2.53, p=0.804) was found. A greater effect of NS seed oil versus seed powder was observed on serum total cholesterol and LDL-C levels, and an increase in HDL-C levels was found only after NS seed powder supplementation. NS has a significant impact on plasma lipid concentrations, leading to lower total cholesterol, LDL-C, and TG levels while increased HDL-C is associated with NS powder only. Further RCTs are needed to explore the NS benefits on cardiovascular outcomes.
The aim of this systematic review and meta-analysis was to evaluate the effects of Nigella sativa (N. sativa) on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress. Two independent authors systematically examined online databases consisting of, EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until October 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of the studied trials. The heterogeneity among the included studies were assessed using the Cochrane’s Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. A total of 50 trials were included in this meta-analysis. We found a significant reduction in total cholesterol (WMD: −16.80; 95% CI: −21.04, −12.55), Triglycerides (WMD: −15.73; 95% CI: −20.77, −10.69), LDL-cholesterol (WMD: −18.45; 95% CI: −22.44, −14.94) and VLDL-cholesterol (WMD: −3.72; 95% CI: −7.27, −0.18) following supplementation with N. sativa. In addition, there was significant reductive effect observed with N. sativa on fasting glucose (WMD: −15.18; 95% CI: −19.82, −10.55) and HbA1C levels (WMD: −0.45; 95% CI: −0.66, −0.23). Effects of N. sativa on CRP (WMD: −3.61; 95% CI: −9.23, 2.01), TNF-α (WMD: −1.18; 95% CI: −3.23, 0.86), TAC (WMD: 0.31; 95% CI: 0.00, 0.63), and MDA levels (WMD: −0.95; 95% CI: −2.18, 0.27) were insignificant. This meta-analysis demonstrated the beneficial effects of N. sativa on fasting glucose, HbA1c, Triglycerides , total-, VLDL-, LDL-cholesterol levels.
Effect of Nigella Sativa on Lipid Profile in Albino Rats
Background: Coronary heart disease is a global health problem. Dyslipidemia is one of its major risk factors. The purpose of this study was to assess the effect of Nigella sativa seeds in the diet on lipid profile in albino rats.
Material and methods: Eighty-four albino rats were divided into six groups. Control groups I, III and V were given; low fat diet with 3% sunflower oil, high fat diet with 20% sunflower oil and high fat diet supplemented with 1% colic acid and 0.5% propylthiouracil as atherogenic elements respectively. The Experimental groups II, IV and VI were given above diets respectively supplemented with Nigella sativa seeds. Lipid profile was estimated at 0, 12 and 24 weeks.
Results: Albino rats fed on low fat diet containing 3% sunflower oil supplemented with Nigella sativa showed significant reduction in TC and LDL cholesterol and rise in HDL cholesterol. Those on high fat diet containing 20% sunflower oil with Nigella sativa seeds showed significant reduction in TG and LDL cholesterol and increase in HDL cholesterol. While in those given high fat diet with 20% sunflower oil, along with 1% cholic acid and 0.5% propylthiouracil with the addition of Nigella sativa, there was significant reduction in TC and LDL cholesterol and rise in HDL cholesterol.
Conclusion: Nigella sativa seeds in the diet has a favorable effect on lipid profile by lowering the Triglyceride , total cholesterol and LDL cholesterol and increasing the HDL cholesterol in albino rats.
Ameliorative effects of Nigella sativa on dyslipidemia
Introduction
Dyslipidemia is an established risk factor for ischemic heart disease. Nigella sativa (NS) is a medicinal plant that has been used for the treatment and prevention of a variety of diseases, in particular hyperlipidemia.
Methods
We reviewed the existing literature published until 2014 by using the following keywords: ‘‘Nigella sativa’’, ‘‘black cumin’’, ‘‘black seeds’’, ‘‘thymoquinone’’, and ‘‘lipid’’.
Results
In the conducted studies, different preparations of NS including seed powder (100 mg–20 g daily), seed oil (20–800 mg daily), thymoquinone (3.5–20 mg daily), and seed extract (methanolic extract especially), were shown to reduce plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and Triglycerides , but the effect on high-density lipoprotein cholesterol (HDL-C) was not significant. NS and thymoquinone have been reported to be safe and well tolerated with no severe adverse effect. In clinical trials, NS was found to be effective when added as adjunct to standard antihyperlipidemic and antidiabetic medications. Lipid-modifying effects of NS could be attributed to the inhibition of intestinal cholesterol absorption, decreased hepatic cholesterol synthesis, and up-regulation of LDL receptors.
Conclusions
Overall, the evidence from experimental and a clinical studies suggests that NS seeds are a promising natural therapy for dyslipidemic patients.
Nigella sativaprovides protection against metabolic syndrome
The seeds of Nigella sativa have been used in folk medicine all over the world. The plant has been of interest due to its low degree of toxicity and beneficial pharmacological properties like antihypertensive, hypoglycemic, antifungal, anti-inflammatory, antihistaminic, antioxidant, along with significant anti-neuplastic activities. The present clinical study was undertaken to ascertain the adjuvant effect of Nigella seeds on various clinical and biochemical parameters of metabolic syndrome. After final diagnosis and considering inclusion and exclusion criteria, one hundred and fifty nine patients were enrolled in this study. Patients were divided into two groups. In Group I (standard group), patients were advised to take simvastatin 10 mg once a day, metformin 500 mg twice a day, Enalapril 10 mg once a day, Atenolol 50 mg once a day and clopidagrel 75 mg once a day for a period of six weeks. In Group II (Nigella seeds group), patients were advised the above standard medication plus Nigella seeds 250 mg twice daily for a period of six weeks. Blood sugar both fasting and postprandial, fasting lipid profile and different parameters of obesity were recorded before therapy and after completion of therapy. It was found that the addition of Nigella seeds provide beneficial effects in all the clinical and biochemical parameters for the adult’s treatment panel-III of metabolic disorders especially in fasting blood sugar, low density lipoproteins and high density lipoproteins. No sign of toxicity of the plant appeared in the Group II. Improvement in all other parameters like blood pressure, circumference of waist and serum Triglyceride was also observed. Thus, Nigella seeds were found to be effective as an adjuvant therapy in patients of dyslipidemia and hyperglycemia.
The aim of the present study was to determine the effects of Nigella sativa (NS) oil on glucose metabolism and lipid concentrations in patients with type 2 diabetes (T2DM). In this double-blind randomized controlled clinical trial, 72 volunteer subjects at Endocrinology Clinics of Kermanshah were recruited. Participants were patients aged 30–60 years old with T2DM. They were randomly divided into intervention (n = 36) and placebo groups (n = 36) and received 3 g/day (one three times a day) NS oil or sunflower soft gel capsules for 12 weeks. At baseline and at the end of the trial, anthropometric indices, dietary intake and biochemical parameters were measured. Sixty-seven patients completed the trial (intervention n = 34, placebo n = 33). Since the data analysis was based on intention-to-treat approach, all 72 subjects (36 in each group) were included for data analysis. Two groups were similar in the baseline characteristics. After the intervention, weight and body mass index decreased in the intervention group compared to the baseline, but it was not significant between the two groups. Dietary intake in both groups changed compared to baseline. Comparison of the two groups indicated that fasting blood sugar, glycated hemoglobin, Triglyceride and low density lipoprotein–cholesterol changed significantly in intervention group compared to the placebo group (p < 0.05, adjusted for confounder factors). Insulin level and insulin resistance decreased and high density lipoprotein–cholesterol increased in the intervention group, but after adjusting for confounder factors, they were not significant. Supplementation with NS oil can improve glycemic status and lipid profile in patients with T2DM.
Blackcurrant (Ribes nigrum) Extract
Blackcurrant extract (BCE)ameliorates dyslipidemia in menopausal model animals and in elderly women at a risk of dyslipidemia. However, it is unknown whether the daily intake of BCE can preventlipid abnormalities in healthy individuals.lipids are essential for the body, but they also cause arteriosclerosis. In this noncomparative pilot study, we examined theeffects of BCE administered for 29 days onserumlipids in young healthy women.blood samples were collected before and on days 4 and 29 after BCE intake, and 20 lipoprotein fractions in theserum were separated using a gel-permeationhigh-performance liquid chromatography method to measure the triacylglycerol andcholesterol levels in lipoproteins. There were noeffects onlipids on day 4 of BCE intake, but the totalcholesterol level decreased on day 29. Furthermore, the levels of total very-low-density lipoprotein (VLDL)cholesterol, small VLDLcholesterol, and large low-density lipoproteincholesterol were significantly decreased. These results suggest that the daily intake of BCE has ahypocholesterolemiceffect in healthy women, and that it iseffective in preventingAtherosclerosis.
Purposes: We previously showed that polyphenol-rich blackcurrant extract (BCE) showed ahypocholesterolemiceffect in mice fed ahigh fatdiet. As directcholesterol removal from the body via the intestine has been recently appreciated, we investigated theeffect of BCE on the modulation of genes involved in intestinalcholesteroltransport using Caco-2 cells as an in vitro model.
Methods: Caco-2 cells were treated with BCE to determine itseffects on mRNA and protein expression of genes important for intestinalcholesteroltransport, low-density lipoprotein (LDL) uptake, cellularcholesterol content, andcholesteroltransport from basolateral to apical membrane of Caco-2 cell monolayers. Cells were also treated with anthocyanin-rich or -poor fraction of BCE to determine the role of anthocyanin on BCEeffects.
Results: BCE significantly increased protein levels ofLDL receptor (LDLR) without altering its mRNA, which consequently increasedLDL uptake into Caco-2 cells. This post-transcriptional induction ofLDLR by BCE was markedly attenuated in the presence of rapamycin, anInhibitor of mechanistic target of rapamycin complex 1 (mTORC1). In addition, BCE altered genes involved incholesteroltransport in the enterocytes, including apical and basolateralcholesteroltransporters, in such a way that could enhancecholesterol flux from the basolateral to apical side of the enterocytes. Indeed, BCE significantly increased the flux ofLDL-derivedcholesterol from the basolateral to the apical chamber of Caco-2 monolayer.LDLR protein levels were markedly increased by anthocyanin-rich fraction, but not by anthocyanin-free fraction.
Conclusion: mTORC1-dependent post-transcriptional induction ofLDLR by BCE anthocyanins drove thetransport ofLDL-derivedcholesterol to the apical side of the enterocytes. This may represent a potential mechanism for thehypocholesterolemiceffect of BCE.
Aim: Obesity is a chronic pathology of epidemic proportions. Mature adipocytes from a 3T3-L1 cell line were used as in vitro obesity model to test different bioactive compounds. We aim to evaluate cassis (Ribes nigrum) extract antioxidant activity and its antiadipogenic effect on mature adipocytes. Results: We produced an extract by using enzyme that combines cellulase and pectinase; we obtained high yield of the bioactive compound anthocyanin. Extract showed high antioxidant capacity. We conducted in vitro assays by adding the extract to adipocytes culture medium. Extract reduced intracellular levels of Triglyceride by 62% and cholesterol by 32%. Conclusion: Enzymatic extract’s high antioxidant activity was likely attributable to its high concentration of anthocyanin. This extract inhibits lipid accumulation in adipocytes.
Estrogen is involved in lipid metabolism. Menopausal women with low estrogen secretion usually gain weight and develop steatosis associated with abnormal lipid metabolism. A previous study showed that blackcurrant (Ribes nigrum L.) extract (BCE) had phytoestrogen activity. In this study, we examined whether BCE improved lipid metabolism abnormalities and reduced liver steatosis in ovariectomized rats, as a menopausal animal model. Twelve-week-old ovariectomized (OVX) rats were fed a regular diet (Ctrl) or a 3% BCE supplemented diet while sham rats were fed a regular diet for three months. Body weight, visceral fat weight, levels of serum Triglycerides , total cholesterol, and LDL cholesterol decreased in the BCE-treated OVX and sham rats, but not in OVX Ctrl rats. The results of hematoxylin and eosin staining revealed that BCE decreased the diameters of adipocytes and the nonalcoholic fatty liver disease activity score. Furthermore, quantitative RT-PCR indicated a decreased expression of hepatitis-related genes, such as tumor necrosis factor-α, IL-6, and IL-1β in OVX rats after BCE treatment. This is the first study that reported improvement of lipid metabolism abnormalities in OVX rats by BCE administration. These results suggest that the intake of BCE alleviated dyslipidemia and prevented nonalcoholic steatohepatitis during menopause in this animal model.
Bulbus Allii Macrostemonis extract
Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol (TC), Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) in serum of rats with hyperlipidemia, increased high-density lipoprotein (HDL-C) levels, and inhibited the expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). According to the findings, 27 active ingredients, such as mandenol, diosmetin and α-spinasterol, might be the main active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs, 16 crosstalk targets and 10 signal pathways might be the main therapeutic targets and pathways, main targeting apolipoprotein A1 (APOA1), apolipoprotein A2 (APOA2), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL), low-density lipoprotein receptor (LDLR) and other crosstalk targets affected cholesterol metabolism, bile secretion, peroxisome proliferator activated receptor (PPAR) signaling pathway in regulating the lipid level, targeting tumor necrosis factor (TNF), IL-6, interleukin-1β (IL-1β), mitogen-activated protein kinase 1 (MAPK1), C-C motif chemokine 2 (CCL2) and other crosstalk targets affected tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway, interleukin-17 (IL-17) signaling pathway, and hypoxia inducible factor (HIF) signaling pathway in regulating the inflammatory factor level.
Bupleurum scorzonerifolium Willd.root extract
The aim of this study was to investigate the antiobesity and antihyperlipidemiceffects of vinegar-baked Radix Bupleuri (VBRB) onhigh-fatdiet- (HFD-) induced obese rats. After being fed HFD for two weeks, rats were dosed orally with VBRB or fenofibrate, once daily for further twelve weeks. VBRB (1.0 g kg−1 per day) producedeffects similar to fenofibrate (100 mg kg−1) inreducing body weight (BW) gain, visceral fat-pad weights, plasmalipid levels, as well as hepatic Triglyceride andcholesterol content of HFD-fed rats. VBRB also lowered hepaticlipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. VBRB and fenofibratereversed the HFD-induced downregulation of hepatic peroxisome proliferator-activated receptor (PPAR)α. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO) and cytochrome P450 isoform 4A1 (CYP4A1) proteins werereversed by VBRB and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats was lowered by VBRB and fenofibrate. The results of this study show that VBRB suppresses BW gain and body fat accumulation by increasing fatty acid oxidation, aneffect which is likely mediated via upregulation of PPARα and downregulation of SREBP expression in the liver of HFD-fed rats.
Saikosaponinsameliorate hyperlipidemia in rats by enhancing hepaticlipid andcholesterol metabolism
Abstract
Ethnopharmacological relevance
Hyperlipidemia is the systemic manifestation of abnormallipidmetabolism, characterized by elevated circulating levels ofcholesterol and Triglyceride and ahigh risk of cardiovascular events. Radix Bupleuri (RB) is a traditional Chinese herbal product used to treat liver diseases. Our previous study demonstrated that Saikosaponins (SSs), the most potent bioactive ingredients in RB,ameliorate hepatic steatosis. However, whether SSs have anti-hyperlipidemiaeffects and plausible underlying mechanisms remain elusive.
Aim of the study
To comprehensively evaluate thelipid-lowering potential of SSs against hyperlipidemia in rats.
Materials and methods
RNA sequencing and untargeted metabolomics approaches were applied to analyze the changes in the liver transcriptome andserumlipid profile in long-termhigh-fatdiet feeding-induced hyperlipidemia rats in response to SSs or positive drug simvastatin (SIM) intervention.
Results
Our data revealed that SSs significantly alleviated HFD-inducedhyperTriglyceride mia and hypercholesterolemia. Combined with the analysis of gene ontology enrichment analysis and gene set enrichment analysis, we found that SSs remarkably repaired the unbalancedbloodlipid metabolic spectrum in a dose-dependent manner by increasing the hepatic uptake of circulating fatty acids and facilitating mitochondrial respiration in fatty acid oxidation, comparable to SIM group. In addition, SSs markedly modulatedcholesterol clearance by promoting intracellularcholesterolefflux, HDL remodeling,LDL particle clearance, and bile acid synthesis. SSs also efficiently protected the liver fromlipid overload-related oxidative stress andlipid peroxidation, as well as substantially exaggerated inflammatory response.
Conclusion
Our research not only unraveled the intricate mechanisms underlying thelipid-lowering functions of SSs but also provided novel perspectives on developing an SSs-based therapeutic strategy for the treatment of hyperlipidemia.
C. pinnatifida Bge fruit Flavones
Theeffects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review
Metabolic syndrome is described as a group of risk factors in which at least three unhealthy medical conditions, including obesity,highblood sugar, hypertension or dyslipidemia occur simultaneously in a patient. These conditions raise the risk for diabetes mellitus and cardiovascular diseases. Many recent studies have focused on herbal remedies and their pharmacologicaleffects on metabolic syndrome. Crataegus pinnatifida or Chinese hawthorn has been widely used in the treatment of hyperlipidemia and cardiovascular diseases. Its leaves, fruits and seeds have various active substances such as, flavonoids, triterpenic acids and sesquiterpenes, which through different mechanisms can be beneficial in metabolic syndrome. Flavonoids found in the leaves of hawthorn can significantly reduce atherosclerotic lesion areas, the fruit extracts contain two triterpenic acids (oleanolic acid and ursolic acid), that have the ability to inhibit the acyl-coA-cholesterol acyltransferase (ACAT) enzyme and as a result reduce very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL)cholesterol levels. Another example regards a sesquiterpene found in the seeds of C. pinnatifida, which exhibits the ability to inhibit platelet aggregation, thus showing antithrombotic activity. Various studies have shown that C. pinnatifida can have beneficialeffects on controlling and treatinghighblood sugar, dyslipidemia, obesity andAtherosclerosis. The aim of this review is tohighlight the interestingeffects of C. pinnatifida on metabolic syndrome.
A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20-60 years with body mass indexes between 25 and 30 kg/m2. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks, the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of Triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals.
Caesalpinia gilleisii Wall et Hook extract
Caesalpinia ferrea C. Mart. (Fabaceae) Phytochemistry, Ethnobotany, and Bioactivities: A Review
Caesalpinia ferrea C. Mart., popularly known as “Jucá” or “Pau-ferro”, belongs to the Fabaceae family, and is classified as a native and endemic species in Brazil. Numerous studies that portray its ethnobotany, chemical composition, and biological activities exist in the literature. The present study aimed to systematically review publications addressing the botanical aspects, uses in popular medicine, phytochemical composition, and bioactivities of C. ferrea. The searches focused on publications from 2015 to March 2020 using the Scopus, Periódicos Capes, PubMed, Google Scholar, and ScienceDirect databases. The leaves, fruits, seeds, and bark from C. ferrea are used in popular medicine to treat disorders affecting several systems, including the circulatory, immune, cardiovascular, digestive, respiratory, genitourinary, musculoskeletal, and conjunctive systems. The most commonly found chemical classes in phytochemical studies are flavonoids, polyphenols, terpenoids, tannins, saponins, steroids, and other phenolic compounds. The biological properties of the extracts and isolated compounds of C. ferrea most cited in the literature were antibacterial, antifungal, antioxidant, antiproliferative, anti-inflammatory, and healing potential. However, further studies are still needed to clarify a link between its traditional uses, the active compounds, and the reported pharmacological activities, as well as detailed research to determine the toxicological profile of C. ferrea.
Caparis decidua. fruit extract
Antiatheroscleroticeffect of Caparis decidua. Fruit Extract incholesterol-fed Rabbits
The fruit alcohol extract of the plant Capparis decidua (Frosk.).. Edgew was investigated for itsAntiatherosclerotic activity. Hyperlipidemia was induced by atherodiet andcholesterol feeding to animals. Rabbits were fed Capparis decidua. (500 mg/kg body weight) or pitavastatin (0.2 mg/kg body weight) in distilled water along with standard laboratorydiet and atherodiet for 60 days. C. decidua. fruit extract and pitavastatin were found to lowerserumcholesterol,LDL-cholesterol, Triglyceride , phospholipid, and atherogenic index, but found to increase the HDL to totalcholesterol ratio as compared with hyperlipidemic control group. Pitavastatin or C. decidua. fruit extract treated hyperlipidemic rabbits showed a decrease in thelipid profile of liver, heart, and aorta. The plant extract feeding brings about a definite regression of atheroma and hindered plaque formation in aorta as compared with the hyperlipidemic control group. Thus, this study demonstrates that C. decidua. fruit extract possesseshypolipidemic andAntiatheroscleroticeffects.
Free fatty acids regulating action of Capparis decidua fruit on dyslipidemia in rats
Capparis decidua belongs to family Capparidaceae in wastelands of India. The study aim was to determine the role of C. decidua fruits on the free fatty acids (FFA) profile in fat-rich diet (FRD) dyslipidemic rats. The methanolic extract of edible fruit of C. decidua (CD) was given orally to obese dyslipidemic rats at the dose of 125 mg/kg and 250 mg/kg for consecutive 28 days. CD treatment in FRD rats significantly restricts the body weight gains. Blood lipid profile was altered dose dependently and significantly after 4-week treatment with CD to FRD. rats. It significantly (p<0.05) enhanced serum FFA especially, -linolinate, -linolinate, arachidonate, ecosapentaenoate, docosapentaenoate and docosahexaenoate. Moreover, 3-PUFA content was also enhanced (50.3% and 78.8%) in the serum of CD treated animals, whereas MUFA was lowered (31.1% and 40%). Therefore, Capparis decidua fruit has a promising role on dyslipidemia and obesity and has the capabilities to regulate beneficial free fatty acids. .
Caralluma fimbriata extract
Antiobesogenic andAntiatherosclerotic Properties of Caralluma fimbriata Extract
There is evidence that the principles present in the widely consumed Indian food plant C. fimbriata extract (CFE) suppress appetite, and provide antiobesogenic and metabolic benefits. Thediet-Induced Obesity (DIO) rat model was used to investigate CFE’s anorexigeniceffects. Rats were randomly divided into three groups: (i) untreated control (C), (ii) control for cafeteriadiet (CA), and (iii) cafeteriadiet fed + CFE treated. Rats in the test group received cafeteriadiet and CFE from day one onwards. CFE was administered by gavage at three doses (25, 50, 100 mg/Kg BW per day) for 90 days. The antiobesogeniceffects of CFE were evaluated by monitoring changes in feed intake, body weight,serumlipid and hormonal (leptin) profiles, fat pads, and liver weight.Antiatheroscleroticeffects were measured by histology. CFE induced significant and dose-dependent inhibition of food intake, with dose-related prevention of gains in body weight, liver weight, and fat pad mass. Alterations inserumlipid profiles associated with weight gain were similarly inhibited, as were the typical increases inserum leptin levels. These data substantiate CFE’s reported anorexigeniceffects. CFE treatment also conferred protection against atherogenesis. We conclude that CFE possesses antiobesogenic andAntiatherosclerotic properties.
The objective of the present study was to investigate the preventive effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) and Metformin (Met) against high-fat diet (HF-diet) induced alterations in lipid metabolism in Wistar rats. The experimental animals were divided into five groups, two of which were fed with chow diet and the other three with HF- (60%) diet. CFE (200 mg/kg body weight/day) was administered through oral route to each group of chow-fed rats, HF-fed rats and Met (20 mg/kg body weight/day) to one of the HF-diet fed groups. At the end of 90 days of experimental period, hypercholestermia, hypertriglycerdemia, with decreased HDL-cholesterol and increased LDL, VLDL-cholesterol and atherogenic index and elevated levels of serum and hepatic transaminases and hepatic lipids (p < 0.05) and alterations in the activities of enzymes of lipid metabolism, and the liver showed mild to severe distortion of the normal architecture as well as prominence and widening of the liver sinusoids as observed in HF-fed rats, were prevented by CFE/Met treatment. The results showed that CFE/Met supplementation ameliorated significantly the disturbance in serum and hepatic transaminases, plasma and hepatic lipid profile and lipid metabolism under HF-fed conditions. It can be concluded from these results that CFE might be valuable in reducing the alterations related to lipid metabolism under high calorie diet consumption.
Antiobesogenic and Antiatherosclerotic Properties of Caralluma fimbriata Extract
There is evidence that the principles present in the widely consumed Indian food plant C. fimbriata extract (CFE) suppress appetite, and provide antiobesogenic and metabolic benefits. The Diet-Induced Obesity (DIO) rat model was used to investigate CFE’s anorexigenic effects. Rats were randomly divided into three groups: (i) untreated control (C), (ii) control for cafeteria diet (CA), and (iii) cafeteria diet fed + CFE treated. Rats in the test group received cafeteria diet and CFE from day one onwards. CFE was administered by gavage at three doses (25, 50, 100 mg/Kg BW per day) for 90 days. The antiobesogenic effects of CFE were evaluated by monitoring changes in feed intake, body weight, serum lipid and hormonal (leptin) profiles, fat pads, and liver weight. Antiatherosclerotic effects were measured by histology. CFE induced significant and dose-dependent inhibition of food intake, with dose-related prevention of gains in body weight, liver weight, and fat pad mass. Alterations in serum lipid profiles associated with weight gain were similarly inhibited, as were the typical increases in serum leptin levels. These data substantiate CFE’s reported anorexigenic effects. CFE treatment also conferred protection against atherogenesis. We conclude that CFE possesses antiobesogenic and antiatherosclerotic properties.
Carnosic Acid (Rosmarinus officinalis)
Rosemary (Rosmarinus officinalis L.) extracts (RE) are natural antioxidants that are used in food, food supplements and cosmetic applications; exert anti-inflammatory and anti-hyperglycaemiceffects; and promote weight loss, which can be exploited to develop new preventive strategies against metabolic disorders. Therefore, the aim of the present study was to evaluate the preventiveeffects of rosemary leaf extract that was standardised to 20 % carnosic acid (RE) on weight gain,glucose levels andlipid homeostasis in mice that had begun ahigh-fatdiet (HFD) as juveniles. The animals were given a low-fatdiet, a HFD or a HFD that was supplemented with 500 mg RE/kg body weight per d (mpk). Physiological and biochemical parameters were monitored for 16 weeks. Body and epididymal fat weight in animals on the HFD that was supplemented with RE increased 69 and 79 % less than those in the HFD group. Treatment with RE was associated with increased faecal fat excretion but not with decreased food intake. The extract also reduced fasting glycaemia and plasmacholesterol levels. In addition, we evaluated theInhibitoryeffects of RE in vitro on pancreatic lipase and PPAR-γ agonist activity; the in vitro findings correlated with our observations in the animal experiments. Thus, the present results suggest that RE that is rich in carnosic acid can be used as a preventive treatment against metabolic disorders, which merits further examination at physiological doses in randomised controlled trials.
Carnosic acid, a new class of lipid absorption inhibitor from sage
The methanolic extract from the leaves of Salvia officinalis L. (sage) showed significant inhibitory effect on serum Triglyceride elevation in olive oil-loaded mice (500 and 1000 mg/kg, p.o.) and inhibitory activity (IC(50): 94 microg/mL) against pancreatic lipase, which is participated in digestion of lipids. Through bioassay-guided separation using the inhibitory activity against pancreatic lipase activity, 4 abietan-type diterpenes (carnosic acid, carnosol, royleanonic acid, 7-methoxyrosmanol) and a triterpene (oleanolic acid) were isolated from the active fraction. Among these compounds, carnosic acid and carnosol substantially inhibited pancreatic lipase activity with IC(50) values of 12 microg/mL (36 microM) and 4.4 microg/mL (13 microM), respectively. Carnosic acid significantly inhibited Triglyceride elevation in olive oil-loaded mice at doses of 5-20 mg/kg (p.o.). However, other constituents (carnosol, royleanonic acid, oleanolic acid) did not show any effects at a dose of 200 mg/kg (p.o.). Furthermore, carnosic acid (20 mg/kg/day, p.o.) reduced the gain of body weight and the accumulation of epididymal fat weight in high fat diet-fed mice after 14 days.
Carnosic acid prevents obesity and hepatic steatosis in ob/ob mice
Aim: Carnosic acid (CA) inhibits adipogenesis in vitro. The present study evaluated the therapeutic effects of CA in ob/ob mice.
Methods: The experimental animals were given a standard chow diet with or without CA for 5 weeks. Bodyweight gain and food intake were measured during this period. Magnetic resonance imaging analysis, histological examination, serum chemistry analysis and intraperitoneal glucose tolerance test (IPGTT) were all performed.
Results: The mice fed CA experienced significant weight loss and reduced visceral adiposity, in addition to significantly reduced serum Triglyceride (TG) and cholesterol levels. Importantly, CA had a dramatic effect on the liver by reducing the hepatic TG content, thus decreasing serum alanine aminotransferase levels. In addition, IPGTT revealed that CA significantly improved glucose tolerance.
Conclusion: These data suggest that CA is a novel therapeutic agent for obesity-related non-alcoholic fatty liver disease.
Carthamus tinctorius extract
FBS, Triglyceride, cholesterol, LDL-C and VLDL-C had a meaningful decrease in diabetic rats treated with Carthamus tinctorius and diabetic rats treated with glibenclamide as compared with diabetic rats with no treatment. Insulin level increased significantly in diabetic groups received treatment (glibenclamide or Carthamus tinctorius L) in comparison with diabetic group with no treatment. The histological study revealed size of islets of Langerhans enlarged significantly consequentially as compared with diabetic rats with no treatment. The extract appeared non toxic as evidenced by normal levels of AST, ALP and ALT. Effects of administrating glibenclamide or extract of Carthamus tinctorius L on all biochemical parameters discussed above showed no difference and both tend to bring the values to near normal.
Cashew leaves (Anacardium occidentale)
Cashew leaves (Anacardium occidentale) is a medicinal plant applied in the treatment of some non-scientific claims of common diseases in SouthWestern Nigeria such as hypertension. It contains phytochemicals such as Phenolic, flavonoids, steroids, triterpenes and 33.52% to 46.26% ofdietary fiber. This work was therefore designed to determine thecholesterolloweringeffect of Cashew leaf (Anacardium occidentale) extract on Egg Yolk Induced Hypercholesterolaemic Rabbits. Fifteen rabbits classified into control group A of five rabbits; experimental group B induced with hypercholesterolemia using 20% egg yolk(B1) and thereafter given cashew leaf ethanolic extract(B2) and group C of five rabbits induced with hypercholesterolemia using 20% egg yolk(C 1) thereafter treated with the aqueous extract of cashew leaf(C 2). Outcomes of biochemical evaluation of experimental rabbits were compared with the control rabbits. Plasma Totalcholesterol(CHOL-T), Low Density Lipoprotein-cholesterol(LDL-C),Total Triglycerides (TG-T),high Density Lipoprotein-cholesterol (HDL-C) were evaluated in the rabbits by autoanalysis using ROCHE reagent on COBAS C111 autoChemistry analyzer. There was a significant increase in plasma totalcholesterol,LDL-C, total Triglycerides and HDL-C when the rabbits were fed with normal meal containing 20% of powdered egg yolk of the total meal weight with water for seven days compared with control rabbits fed on normaldiet and water for 7 days with p<0.05. A significant decrease was also obtained in plasma Totalcholesterol and Total Triglycerides in the rabbits given 400mg/Kg of either ethanolic or aqueous extract of cashew leaves extract after they were being given 20% of powdered egg yolk of the total meal weight plus water for seven days which was more in ethanolic extract than the aqueous extract with p<0.05. There was also a significantly lowerLDL-C in rabbits fed with normal meal containing 20% of powdered egg yolk of the total meal weight plus water for seven days followed by the administration of 400mg/Kg of ethanolic extract for another seven days. than when the rabbits were fed with normal meal containing 20% of powdered egg yolk of the total meal weight with water for seven days and also than in the rabbits induced with hypercholesterolemia using20% of powdered egg yolk of the total meal weight followed by aqueous cashew leaf extract (p<0.05). This work revealed the efficacy of 20% egg yolk at inducing hypercholesterolaemia while ethanonolic and aqueous extract have been found to decrease plasma levels of CHOL-T, TG-T andLDL-C and as such could be applied in the treatment of hypertecholesterolaemia which may result into hypertension.
Extract of the Anacardium occidentale leaves is used in the traditional treatment of diabetic diseases. The hypoglycemic effect of leaves aqueous extract was investigated using normoglycemic albino rats. The leaves aqueous extract was found to contain phytochemicals such as alkaloids, saponins, flavonoids and tannins. The aqueous extract significantly lowered the blood glucose concentration in the normal rats (p> 0.05). The extract produced about 33.7 % (305 ± 2.89 to 202 ± 4.04) mg/dl. The serum Triglyceride decreases by 48.28 % (435± 4.50 to 225 ± 1.50) mg/dl in the experimental rats. While serum total protein decreases by 18.41% (27.7 ± 2.54 to 22.6 ± 0.32) g/d and weight increase was 4.75 % (134.6 ± 5.02 to 128.5 ± 1.15) g. The result obtained indicated that the extract has a moderate hypoglycemic effect and may be used locally for the treatment of diabetes mellitus.
Celastrus Orbiculatus Thunb.
Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed ahigh-fatdiet, and increaseshigh-density lipoprotein (HDL). In the present study, we investigated theeffect of COT inreducinglipid accumulation and promotingreversecholesteroltransport (RCT) in vivo and vitro. Healthy male mice were treated withhigh-fatdiet alone,high-fatdiet with COT (10.0 g/kg/d), or general fodder for 6 weeks.serum levels of totalcholesterol (TC), Triglyceride (TG), HDL-C, non-HDL-C, and 3H-cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and Triglyceride in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reducedlipid accumulation in the liver,ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non-HDL-C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL-C andapolipoprotein A (apoA1). 3H-cholesterol in plasma, liver, bile, and feces was also significantly increased in COT-treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1,LDLR, ATP-binding cassettetransporters ABCA1, ABCG5, and LXRα wereimproved in COT-treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased theefflux of 3H-cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT inreducinglipid accumulation by promoting RCT. Theseeffects may be achieved by activating the SRB1 and ABCtransporter pathway and promotingcholesterolmetabolism via the CYP7A1 pathway in vivo. Theeffective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin.
Celastrus orbiculatus Thunb. (COT) is a traditional Chinese herb. In this study, an experiment was designed to investigate the potential protective effect of COT on the development of non-alcoholic fatty liver disease (NAFLD) induced by high fat diet and to explore the underlying mechanisms. We established a guinea pig model of NAFLD and treated the animals with three doses of COT or 20 mg/kg/d simvastatin (a positive control drug) for 8 weeks. H&E staining of liver tissue sections indicated that COT remarkably improved histopathological change of liver induced by high fat diet. Serum biochemical assays revealed that COT significantly decreased ALT and AST activities in serum. Besides, COT also reduced body weight and liver weight of guinea pigs under high fat diet. Hepatic lipid analysis showed that COT remarkably decreased the contents of total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE) and Triglyceride (TG) in liver of guinea pigs fed high fat diet in a dose-dependent manner. The analysis of hepatic genes involved in cholesterol metabolism by quantitative real-time PCR revealed that COT upregulated the mRNA abundance of cholesterol 7alpha-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Measurement of biochemical parameters in liver indicated that COT attenuated oxidative stress and lowered NO and iNOS levels in guinea pigs under high fat diet. These results reveal that administration of COT effectively ameliorates high-fat diet-induced NAFLD in guinea pigs through decreasing hepatic lipid levels, suppressing oxidative stress and lowering NO and iNOS levels in liver.
chalcone derivative, 1m-6
Background and Purpose
Atherosclerosis, resulting fromlipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess beneficial properties, including anti-inflammatory, antioxidant and antitumour activity with unknown cardioprotectiveeffects. We aimed to develop aneffective chalcone derivative with antiatherogenic potential.
Experimental Approach
Human THP-1 cells and HUVECs were used as in vitro models. Western blots and real-time PCRs were performed to quantify protein, mRNA and miRNA expressions. Thecholesterolefflux capacity was assayed by 3H labelling ofcholesterol.LDL receptor knockout (LDLR−/−) mice fed ahigh-fatdiet were used as an in vivo atherogenesis model. Haematoxylin and eosin and oil red O staining were used to analyse plaque formation.
Key Results
Using ATP-binding cassettetransporter A1 (ABCA1) expression we identified the chalcone derivative, 1m-6, which enhances ABCA1 expression and promotescholesterolefflux in THP-1 macrophages. Moreover, 1m-6 stabilizes ABCA1 mRNA and suppresses the expression of potential ABCA1-regulating miRNAs through nuclear factor erythroid 2-related factor 2 (Nrf2)/haem oxygenase-1 (HO-1) signalling. Additionally, 1m-6 significantly inhibits TNF-α-induced expression of adhesion molecules, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), plus production of proinflammatory cytokines via inhibition of JAK/STAT3 activation and the modulation of Nrf2/HO-1 signalling in HUVECs. InAtherosclerosis-prone mice, 1m-6 significantly reduceslipid accumulation and atherosclerotic plaque formation.
Conclusion and Implications
Our study demonstrates that 1m-6 produces promising atheroprotectiveeffects by enhancingcholesterolefflux and suppressing inflammation-induced endothelial dysfunction, which opens a new avenue for treating ASCVD.
Chenodeoxycholic acid (CDCA)
Background: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepaticcholesterol and bile acid synthesis and reduces biliarycholesterol secretion and Triglyceride production. Animal studies have shown that bile acids downregulate hepaticLDL receptors (LDLRs); however, information onLDLmetabolism in humans is limited.
Methods: Kinetics of autologous 125 I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg-1 day-1 ). In seven patients with gallstones treated with CDCA for 3 weeks before cholecystectomy, liver biopsies were collected and analysed for enzyme activities and for specificLDLR binding.serum samples obtained before treatment and at surgery were analysed for markers oflipidmetabolism, lipoproteins and theLDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9).
Results: Chenodeoxycholic acid treatment increased plasmaLDLcholesterol by ~10% as a result of reduced clearance of plasmaLDL-apolipoprotein (apo)B;LDL production was somewhat reduced. The reduction inLDL clearance occurred within 1 day after initiation of treatment. In CDCA-treated patients with gallstones, hepatic microsomalcholesterol 7α-hydroxylase and HMG-CoA reductase activities were reduced by 83% and 54%, respectively, and specificLDLR binding was reduced by 20%. During treatment,serum levels of fibroblast growth factor 19 and total andLDLcholesterol increased, whereas levels of 7α-hydroxy-4-cholesten-3-one, lathosterol,PCSK9, apoA-I, apoC-III, lipoprotein(a), Triglycerides and insulin were reduced.
Conclusions: Chenodeoxycholic acid has a broad influence onlipidmetabolism, includingreducing plasma clearance ofLDL. The reduction in circulatingPCSK9 may dampen itseffect on hepaticLDLRs and plasmaLDLcholesterol. Further studies of theeffects of other FXR agonists oncholesterolmetabolism in humans seem warranted, considering the renewed interest for such therapy in liver disease and diabetes.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy inreducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a)lowering.
Theeffects on biliarylipids of 10 mg per kg per day of chenodeoxycholic acid (CDCA), 10 mg per kg per day of ursodeoxycholic acid (UDCA), and their equimolar combination (5 mg per kg per day of each), all administered for 45 to 60 days, were investigated in 18 patients with gallstones in a double-blind study with a balanced latin square design. The molar percentage ofcholesterol in bile (initial value 9.7 ± 2.2) was significantly lower after UDCA (5.4 ± 1.3) and the combination (5.2 ± 1.2) than after CDCA (7.2 ± 1.7).
Nevertheless, when the ability to solubilizecholesterol was calculated, taking into account the percentage of biliary UDCA, then the differences incholesterol saturation induced by UDCA alone and the combination also became considerable (saturation index: 0.94 ± 0.12 as compared to 0.81 ± 0.12).
The total bile acid pool increased significantly after treatment with CDCA and the combination, but not after UDCA. Lithocholic acid was increased significantly only by treatment with CDCA.
Diarrhea was observed in five patients with hypertransaminasemia and in four patients after CDCA, whereas both UDCA and the combination were well-tolerated.
We conclude that the administration of a combination of equimolar doses of CDCA and UDCA can be recommended for medical treatment of gallstones since it has greatereffects on bilecholesterol saturation than either alone, is better tolerated than CDCA, and is less expensive than UDCA.
The effects of chenodeoxycholic acid (C.D.C.A.) therapy on plasma lipid and lipoprotein metabolism have been studied in eleven patients with hypertriglyceridæmia. Plasma-Triglycerides fell significantly by 79-986 mg. per 100 ml. (25-54%) in nine of the patients, the absolute fall being positively correlated with the pretreatment concentration. The Triglyceride -lowering effect of C.D.C.A. appeared to derive from a decreased secretion into plasma of the Triglyceride -rich very-low-density lipoprotein. Three patients also demonstrated relatively smaller falls (14-28%) in plasma-cholesterol. Treatment was well tolerated, although in nine patients the serum activities of aspartate and alanine amino-transferases rose slightly. Long-term clinical trials of C.D.C.A. in the treatment of hypertriglyceridæmia seem to be indicated.
Chenodeoxycholic acid therapy for hypertriglyceridaemia in men
Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum Triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and thereafter monthly for a further 6 months on clofibrate 2 g daily. 2 The mean serum Triglyceride level fell by 36% after dietary treatment alone (P less than 0.05) and by 47% from initial values on diet plus chenodeoxycholic acid (P less than 0.01). In the nine patients who proceeded to clofibrate therapy there was a rise in Triglyceride levels on placebo capsules to the level achieved by diet alone, and a further fall on diet plus clofibrate of 47% of initial values (P less than 0.05). 3 Chenodeoxycholic acid therapy is effective in the management of hypertriglyceridaemia not completely cured by dietary measures, and may be as efficacious as clofibrate.
Chinese Taxillus Twing extract
Chinese medicinal composition for treating hyperlipidemia
Chinese angelica nourishes blood and invigorates blood circulation; the szechwan lovage rhizome dredges meridians and removes stasis; the safflower invigorates blood circulation and removes stasis; the peach kernel breaks blood and removes stasis, and relaxes bowl; the zedoary can promote the circulation of qi and remove stasis in blood; and the combined application of the medicaments can make total cholesterol (TC) and/or Triglyceride (TG) or high-density lipoprotein cholesterol (HDL-C) in the blood within the range of normal values so as to ensure that the metabolism or operation of blood fat is normal.
Chitosan
This study presents a meta-analysis of studies that investigate theeffectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate theeffect of chitosan supplementation. Theeffect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity ofeffect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity ofeffect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated,blood Triglyceride and HDL-cholesterol showed thehighest heterogeneity, respectively. Other thanblood HDL-cholesterol, totalcholesterol, and Triglyceride in feces, most items evaluated showed a negativeeffect size withhigh significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be mosteffective inlowering body weight. In addition, chitosan supplementation proved to be aneffective solution forserum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise inreducing the risk ofcholesterol related metabolic disorder.
Properties of nanopowdered chitosan and itscholesterolloweringeffect in rats
This study was carried out to compare the properties of nanopowdered chitosan (NPC) to commercially powdered chitosan (CPC) and examine theeffect of NPC onserum and livercholesterollowering in rats. Twentyfour male rats of Sprague-Dawley strain were blocked into 3 groups and were raised for 8 weeks.highcholesteroldiet, 2% CPC, or 2% NPC were given to 3 groups. NPC reduced totalcholesterol by 46.6% and CPC reduced it by 18.6%. NPC also significantly reduced low density lipoprotein (LDL)-cholesterol by 55.7%, while CPC reduced by 36.8%.high density lipoprotein (HDL)-cholesterol content was increased more with NPC by 16.5% than with CPC by 9.6%. Triacylglycerol content was also decreased significantly by 42.8% with NPC, while reduced by 22.5% with CPC. The present study indicated that NPC feeding reduced total andLDL-cholesterol and triacylglycerol contents and increased HDL-cholesterol content.
Effects of Chitosan on Plasma Lipids and Lipoproteins: A 4-Month Prospective Pilot Study
Chitosan can favorably modulate plasma lipids, but the available data are not conclusive. We evaluated the effect of chitosan on plasma lipids and lipoproteins in 28 patients with plasma Triglyceride levels >150 mg/dL (mean age: 63 ± 12 years), not taking other lipid-lowering agents. All patients received a chitosan derived from fungal mycelium (Xantonet, Bromatech, Italy) at a fixed dose of 125 mg/d in addition to their current medications for 4 months. Polyacrylamide gel electrophoresis was used to measure low-density lipoprotein (LDL) subclasses. After treatment, total cholesterol reduced by 8%, LDL cholesterol by 2%, and Triglycerides by 19%, with a concomitant 14% increase in high-density lipoprotein cholesterol. We also found a beneficial effect of chitosan on LDL subclasses, with a significant increase in LDL-2 particles (from 37 ± 8% to 47 ± 8%, P = .0001) and a decrease (although not significant) in atherogenic small, dense LDL. Whether these findings may affect cardiovascular risk remains to be established in future studies.
Cholesterol-lowering properties and safety of chitosan
Chitosan (CAS 9012-76-4) is derived by alkaline deacetylation from chitin, an abundant polymeric product of natural biosynthesis especially in crustaceans. It is available in a primary, unorganised structure, but also in a microcrystalline form. As a dietary supplement, chitosan has been claimed to control obesity and to lower serum cholesterol. A variety of chitosan products have been freely available worldwide in health stores and pharmacies. This review summarises the current knowledge about cholesterol-lowering and safety properties of chitosan and focuses its possible application for the treatment of hypercholesterolaemia. Chitosan behaves as a polycationic(+) cellulose-like fibrillar biopolymer that forms films with negatively charged surfaces. It is not specifically hydrolysed by digestive enzymes in man, but limited digestion of chitosan due to bacterial flora and to the unspecific enzymes might occur. Negatively charged molecules in stomach attach strongly to the positive charged tertiary amino group (-NH3+) of chitosan. Therefore, chitosan reduces fat absorption from gastrointestinal tract by binding with anionic carboxyl groups of fatty and bile acids, and it interferes with emulsification of neutral lipids (i.e., cholesterol, other sterols) by binding them with hydrophobic bonds. In short-term animal studies the safety of chitosan has been good. There are only few studies with chitosan in humans. In man, dietary chitosan has been reported to reduce serum total cholesterol levels by 5.8-42.6% and low-density lipoprotein levels by 15.1-35.1%. In short-term trials up to 12 weeks, no clinically significant symptoms have been observed with chitosan compared to placebo. Mild and transitory nausea and constipation have been reported in 2.6-5.4% of subjects. Although chitosan has been clinically well tolerated, it cannot be recommended to people allergic to crustaceans.
This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated, blood Triglyceride and HDL-cholesterol showed the highest heterogeneity, respectively. Other than blood HDL-cholesterol, total cholesterol, and Triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for serum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in reducing the risk of cholesterol related metabolic disorder.
Cichorium intybus L. var. foliosum Hegi extract
Antioxidativeeffects of cichorium intybus root extract on LDL (low density lipoprotein) oxidation
The water extract of Cichorium intybus (WECI) showed a remarkable antioxidativeeffect onLDL, andInhibitoryeffects on the production of thiobarbituric acid reactive substance and the Degradation of fatty acids inLDL. Vitamin E and unsaturated fatty acids inLDL were protected by adding WECI from theeffects of metal catalyzedLDL oxidation. From the results obtained, we conclude thatLDL oxidation is inhibited in vitro by the addition of WECI, and thatLDL is protected by WECI from oxidative attack, as shown by agarose gel electrophoresis.
Effect of Cichorium intybus L. on fatty liver induced by oxytetracycline in albino rats.
Results: Fatty liver groups showed high significant increase in serum glucose, cholesterol, Triglycerides, LDL cholesterol, ALAT, ASAT, GGT, LDH, urea, creatinine and A/G ratio while total protein, albumin, globulin and HDL cholesterol were significantly decreased compared to control group. These biochemical changes were accompanied with histopathological alterations in fatty liver tissue. The treatment with chicory ameliorated most of the evaluated biochemical parameters and improved the induced degenerative histopathological changes. The pre-treatment with chicory before the induction of fatty liver gave some protection against factors that experimentally induced fatty liver.
Conclusion: Chicory as diet additive is recommend for fatty liver patients or those people who have hyperlipidemic family history.
Diabetes mellitus is associated with increased levels of inflammation and oxidative stress in patients. The aim of the present study was to test the hypothesis that aqueous extract of Cichorium intybus seeds (AECIS) would have add-on beneficial effect in type 2 diabetes mellitus (T2DM). In this double-blind randomized clinical study, 150 subjects were enrolled to assess the add-on efficacy and safety of AECIS in T2DM patients. The subjects were randomized (1:1) to the AECIS (n = 51) and placebo (n = 49) groups. The subjects in both groups continued to take prescribed doses of metformin. The standardization of AECIS was carried out by liquid chromatography–mass spectrometry and phytochemical analysis. The mean hemoglobin A1c (HbA1c) level in the AECIS and placebo groups at baseline was 8.6% and 8.5%, respectively. Mean values of HbA1c at the end of 12 weeks of intervention were 7.42% in the AECIS group (a reduction of 1.18% from baseline) and 8.4% in the placebo group (mean reduction of 0.1% from baseline). Besides, significant reduction in inflammation, oxidative stress, and hyperTriglyceridemia was seen in the AECIS group (p < .05). The study shows for the first time that AECIS supplementation ameliorates the disease progression and it is beneficial as a potential adjunct dietary supplement for the management of T2DM.
Cinnamomum Zeylanicum bark
Introduction
Atherosclerosis is one of the major causes of disability ofblood vessels which can result in development of many cardiovascular disorders. There is a strong association betweenAtherosclerosis and insulin resistance and dyslipidemia.
Aim
To study theAnti-atherosclerotic potential of C. zeylanicum bark extract in insulin resistance associatedAtherosclerosis and worsened Atherogenic Index (AI) associated with dyslipidemia, which are the predominant complications of steroid diabetes in Wistar rats.
Materials and Methods
A sum of 36 rats were categorized into five study groups and one plain control. In a 12 day study period, respective drug treatments were given every day throughout the study period whereas, dexamethasone dosage was started from day seven onwards. On day 12, fastingblood samples were collected and processed forlipid estimation and the determined values were also used to assess AI further. Animals were sacrificed under ether anaesthesia and the aorta was dissected away for its measurement and histopathological findings. One-way ANOVA was used to analyse the data and multiple comparison was done, interpreted based on Post-Hoc Scheffe test.
Results
high dose of dexamethasone (8 mg/kg/i.p) in Dexa Control (DC) group produced significant dyslipidemia, increased risk of atherogenicity (p<0.05) and caused severe thickening (78.5% compared to Plain Control (PC) of wall of aorta. Rosiglitazone (ROSI) (8 mg/kg and 16 mg/kg) and C. zelanicum (CZE) extract treatments (500 mg/kg and 250 mg/kg) significantly prevented dyslipidemia, well maintained AI compared to dexa control (p<0.05). However, both the CZE treatments protected the aorta fromAtherosclerosis (40.3% and 30.2% compared to DC) and significantly prevented the dyslipidemia and reduced the risk of atherogenicity compared to ROSI treatment (p<0.05). Although, the CZE did not show difference in significance in maintaining very low density lipoprotein when compared to ROSI (p>0.05). The atherosclerotic changes were completely absent in both the CZE treatments whereas, ROSI treatments did not prevented theAtherosclerosis of aorta completely as they showed moderate and mild atherosclerotic changes in the aorta.
Conclusion
The aqueous extract of C. zelanicum bark exhibited marked protection against dexamethasone inducedAtherosclerosis and also minimized the atherogenic risk in Wistar rats.
Purpose
According to the World Health Organization (WHO), approximately 150 million people worldwide have type 2 diabetes. It is a growing health concern. Common and cassia cinnamon have been reported to have anti-diabetic andlipid-lowering effects. The objective was to determine if the combination of common and cassia cinnamon (Cinnamomum verum and C. aromaticum) reduces fastingbloodglucose, insulin, glycosylated hemoglobin (HA1C), Triglyceride , totalcholesterol, HDLcholesterol andLDLcholesterol levels in people with type 2 diabetes.
Methods
Fifty (50) type 2 diabetic participants were randomized to receive either 140 mg of Cinnamonforce twice daily or placebo over 13 weeks. Physical and laboratory measurements were taken at baseline, 2 weeks, 4 weeks, 8 weeks and at the end of the trial, 13 weeks.
Results
There were no significant improvements in fastingglucose, insulin andlipid parameters between treatment and placebo groups. At endpoint, subjects in the treatment group were found to have a marginally non-significanthigher fastingbloodglucose level than subjects taking the placebo (p=0.085). There was a non-significant decrease in HA1c in the treatment group versus the placebo group (p=0.172). In secondary outcomes, significant differences in weight (p= 0.008), BMI (p= 0.001) and waist-to-hip ratio (p=0.020) were detected in the treatment versus placebo groups.
Conclusion
The combination of common and cassia cinnamon do not impact fastingglucose, insulin andlipid measurements. Through power calculations, there may be aneffect on HA1c, however, the sample size in this study was not sufficient to detect a trend, if any. Although secondary outcomes in this study, common and cassia cinnamon should be further investigated for weight loss.
Lipid lowering effect of Cinnamomum zeylanicum in hyperlipidaemic albino rabbits
The purpose of the present study was to investigate the lipid lowering effect of Cinnamomum zeylanicum (Cinnamon) in hyperlipidaemic albino rabbits. For this purpose, forty eight albino rabbits were randomly divided into eight equal groups; untreated control on normal routine feed, untreated control on butter and cholesterol, treated control on synthetic cholesterol lowering drug simvastatin (Tablet survive (R) 20 mg), three treated groups on three respective doses of C. zeylanicum bark powder and two treated groups on water and methanol extracts of C. zeylanicum bark powder. Butter ad lib and cholesterol powder 500 mg/kg body weight were used to induce experimental hyperlipidaemia in all groups except untreated control group. The results suggested that C. zeylanicum bark powder at the rate of 0.50 g/kg, 0.75 g/kg and methanol extract equivalent to 0.75 g/kg powder produced respective percent reductions in total lipids by 45, 49 and 64; Triglycerides by 38, 53 and 60; total cholesterol by 53, 64 and 69 and LDL-cholesterol by 50, 59 and 62. However, at these dosage levels HDL-cholesterol showed respective percent increase of 42, 48 and 53. Nonetheless, C. zeylanicum bark powder at the level of 0.25g/kg and C. zeylanicum extract in water could not significantly reduce lipid profile indicators. Based on these studies, it can safely be said that C. zeylanicum bark powder methanol extract equivalent to 0.75g/kg bark powder and simvastatin (0.6 mg/kg b. wt.) were equieffective in treating hyperlipidaemia.
Clerodendrum minahassae
Leilem, which is known with the botanical name Clerodendrum minahassae, is a plant species commonly used as a component of almost all meat- and fish-based cuisine. In addition to enhancing the flavor and taste suited to the local people, leaves of leilem is also believed to possesshigh level of natural antioxidant. The leaves of this plant has also been used as traditional medicine to treat stomachache and lung diseases. Our previous study revealed that ethanol extract of leilem has beneficial antihyperlipidemic andAntiatheroscleroticeffects on the aorta of Wistar rats fed withhighlipid andcholesterol levels. The present study was aimed at investigating the phytochemical contents and antioxidant activity of ethanol extract of leilem leaves. Phytochemical screening was carried out using standard methods of precipitation and coloration reactions. In addition, the total phenolics and flavonoids were determined by using spectrophotometric methods. Finally, the leaf extract of leilem was assayed to evaluate its in vitro antioxidant properties using 1,1-Diphenyl picryl hydrazyl (DPPH) radical assay and ferricreducing antioxidant potential (FRAP) assay. The phytochemical screening of leilem leaves revealed the presence of alkaloids, saponins, flavonoids, steroids, and phenols, while terpenes and tannins were not detected. The extract of leilem leaves showed estimated phenolics and flavonoid content of 139.88 mg/g and 34.46 mg/g respectively. Concentration of leilem leave extract required for 50% inhibition of DPPH radical scavengingeffect (IC50) was recorded as 565.45 μg/mL. At 1 mg/mL concentration, the aqueous extract of leilem leaves showed ferricreducing power of 123.62 μmoles/mg in FRAP assay. These findings suggest that the ethanol extract of leilem has potential in vitro antioxidant activities. Overall, results obtained from this study support our previous finding that the extract of leilem leaves has beneficial antihyperlipidemic andAntiatheroscleroticeffects and can be used as an alternative to synthetic antioxidants.
Our previous study revealed that ethanol extract of leilem has beneficial antihyperlipidemic and antiatherosclerotic effects on the aorta of Wistar rats fed with high lipid and cholesterol levels. Extract of leilem leaves was able to decrease Triglyceride levels as well as increase HDL levels. Moreover, it also improved the aorta by reducing the number of foam cells and the thickness of the aortic wall. The purpose of this study was to investigate the phytochemical contents and antioxidant activity of ethanol extract of leilem leaves.
Codonopsis pilosula (Franch.)Nannf.root extract
effects of Codonopsis pilosula crude polysaccharides by hypoglycemic and modulating gut microbiome in ahigh-fatdiet and streptozotocin-induced mouse model of T2DM
The study explored the nature and structure of ultrasonically extracted Codonopsis pilosulae crude polysaccharides (CPCPs) and theeffects of CPCPs on hypoglycemiceffects and gut flora in ahighglucose andhigh-fat feeding and STZ-induced T2DM mice model. The results showed that the CPCPs consisted mainly of polysaccharides, uronic acids, proteins and SO42−. CPCPs consisted of β-type pyranose and exhibited porous, irregular fibrillation and aggregation, and inhibited the activity of α-amylase and α-glucosidase. 1 g/kg CPCPs reduced diabetic symptoms, including modulation of body weight andblood biochemistry levels, reducedblood sugar andlipids, liver, kidney, pancreas indices, oxidative damage and inflammatory factor levels in T2DM mice. For diabetic mice gut microbes, 1 g/kg CPCPs reduced the ratio of Firmicutes and Bacteroidetes; at the genus level and reduced Enterobacter abundance and increased Bacteroides abundance. These results suggested that CPCPs may beeffective supplements for preventing or treating of T2DM.
Protective Effect of Codonopsis lanceolata Root Extract Against Alcoholic Fatty Liver in the Rat
Alcohol intake remains the most important cause of fatty liver throughout the world. The current study was undertaken to determine whether dietary supplementation with Codonopsis lanceolata root water extract attenuates the development of alcoholic fatty liver in rats and to elucidate the molecular mechanism for such an effect. Male Sprague-Dawley rats were fed normal diet (ND), ethanol diet (ED) (36% of total energy from ethanol), or 0.5% C. lanceolata root extract-supplemented ethanol diet (ED+C) for 8 weeks. C. lanceolata root water extract supplemented to rats with chronic alcohol consumption ameliorated the ethanol-induced accumulations of hepatic cholesterol and Triglyceride. Chronic alcohol consumption up-regulated the hepatic expression of genes involved in inflammation, fatty acid synthesis, and cholesterol metabolism, including tumor necrosis factor α (TNFα), liver X receptor α (LXRα), sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase, acetyl-coenzyme A carboxylase α (ACC), stearoyl-coenzyme A desaturase 1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), and low-density lipoprotein receptor (LDLR). The ethanol-induced up-regulations of TNFα, LXRα, SREBP-1c, HMGR, and LDLR genes in the liver were reversed by feeding C. lanceolata root water extract for 8 weeks. Moreover, ethanol-induced decreases in the ratio of phospho-5′-AMP-activated protein kinase (AMPK) α/AMPKα and phospho-ACC/ACC protein levels in the liver were significantly restored (135% and 35% increases, respectively, P < .05) by supplementing them with C. lanceolata root water extract. In conclusion, C. lanceolata root water extract appears to be protective against alcoholic fatty liver through the regulation of SREBP-1c, LXRα, HMGR, and LDLR genes and by the phosphorylation of AMPKα and ACC, which are implicated in lipid metabolism.
A homogeneous polysaccharide coded as CPP−1 was extracted and purified from the root of Codonopsis pilosula (Franch.) Nannf. by water extraction, ethanol precipitation, and column chromatography. Its structure was analyzed by HPGPC-ELSD, HPLC, GC-MS, FT-IR, and NMR techniques. The results indicated that CPP−1 was composed of mannose (Man), glucose (Glc), galactose (Gal), and arabinose (Ara) at a molar ratio of 5.86 : 51.69 : 34.34 : 8.08. The methylation analysis revealed that the main glycosidic linkage types of CPP−1 were (1→)-linked-Glc residue, (1→3)-linked-Glc residues, (1→4)-linked-Gal residue, (1→2,3,4)-linked-Glc residue, (1→)-linked-Man residue, (1→3,4)-linked-Glc residue, and (1→)-linked-Ara residue. In vivo efficacy trial illustrated that CPP−1 supplements could alleviate HFD-induced mice obesity significantly, as well as improve obesity-induced disorders of glucose metabolism, alleviate insulin resistance, and improve the effects of lipid metabolism. The findings indicate that this polysaccharide has the potential for the treatment of obesity.
Coenzyme Q10
Context: Previous meta-analyses have suggested that theeffects of coenzyme Q10 (CoQ10) onlipid profiles remain debatable. Additionally, no meta-analysis has explored the optimal intake of CoQ10 for attenuatinglipid profiles in adults.
Objective: This study conducted a meta-analysis to determine theeffects of CoQ10 onlipid profiles and assess their dose-response relationships in adults.
Methods: Databases (Web of Science, PubMed/Medline, Embase, and the Cochrane Library) were systematically searched until August 10, 2022. The randomeffects model was used to calculate the mean differences (MDs) and 95% CI for changes in circulatinglipid profiles. The novel single-stage restricted cubic spline regression model was applied to explore nonlinear dose-response relationships.
Results: Fifty randomized controlled trials with a total of 2794 participants were included in the qualitative synthesis. The pooled analysis revealed that CoQ10 supplementation significantly reduced totalcholesterol (TC) (MD -5.53 mg/dL; 95% CI -8.40, -2.66; I2 = 70%), low-density lipoproteincholesterol (LDL-C) (MD -3.03 mg/dL; 95% CI -5.25, -0.81; I2 = 54%), and Triglycerides (TGs) (MD -9.06 mg/dL; 95% CI -14.04, -4.08; I2 = 65%) and increasedhigh-density lipoproteincholesterol (HDL-C) (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%). The dose-response analysis showed an inverse J-shaped nonlinear pattern between CoQ10 supplementation and TC in which 400-500 mg/day CoQ10 largely reduced TC (χ2 = 48.54, P < .01).
Conclusion: CoQ10 supplementation decreased the TC,LDL-C, and Triglyceride levels, and increased HDL-C levels in adults, and the dosage of 400 to 500 mg/day achieved the greatesteffect on TC.
The Redox Status of Coenzyme Q10 in TotalLDL as an Indicator of In Vivo Oxidative Modification
Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, denseLDL particles that have been found to be more prone to oxidative modification. We isolated totalLDL as fresh as possible from 12 normolipidemic relatives with a buoyantLDL subfraction profile (group 1), 7 normolipidemic subjects with a denseLDL subfraction profile (group 2), and 16 hyperlipidemic FCH subjects with a denseLDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resistance of totalLDL against Cu2+-oxidation in vitro. In addition, we analyzed the α-tocopherol and the coenzyme Q10 contents ofLDL and determined their relation toLDL oxidizability.LDL isolated from group 3 subjects was more susceptible to oxidative modification thanLDL from group 1 subjects (lag time: 60.4±8.1 versus 70.4±11.4 minutes; P<.05). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids inLDL, together with the basal amount of dienes inLDL, were good predictors of the rate ofLDL oxidation (R2=.73, P=.0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to α-tocopherol inLDL were reduced compared with group 1 (P<.05). The K-value, a measure of theLDL density, correlated with the the redox status (r=.37, P<.05). We conclude that in subjects with FCH totalLDL is more prone to oxidation, due to the predominance of denseLDL particles. In addition, the decreased redox status of coenzyme Q10 inLDL from subjects with a denseLDL subfraction profile suggests that theLDL in the circulation has already undergone some oxidation.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy inreducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a)lowering.
Results and discussion
Seven trials were included in the meta-analysis, involving 356 patients. Neither CoQ10 alone nor CoQ10 plus fenofibrate improved glycemic control. In addition, CoQ10, alone or in combination with fenofibrate, did not alter LDL-C, HDL-C and blood pressure. Triglycerides levels were significantly reduced with CoQ10 (mean difference −0·26 mmol/L, 95% CI −0·05 mmol/L to −0·47 mmol/L, P = 0·02) and CoQ10 plus fenofibrate (mean difference −0·72 mmol/L, 95% CI −0·32 mmol/L to −1·12 mmol/L, P = 0·0004). CoQ10 plus fenofibrate also effectively reduced total cholesterol (mean difference: −0·45 mmol/L, 95% CI −0·06 mmol/L to −0·84 mmol/L, P = 0·02).
What is new and conclusions
CoQ10 supplementation has no beneficial effects on glycemic control, lipid profile or blood pressure in patients with diabetes. However, it may reduce Triglycerides levels. Due to limited data availability, well-powered and well-designed randomized controlled trials are needed to clearly determine the effect of CoQ10 on metabolic profile in diabetes. Dosage effects should also be explored.
Results
All 101 subjects were included in the analysis. On the 12th week, compared to placebo, CoQ10 supplementation decreased systolic (P = .010) and diastolic pressure (P = .001) and increased serum total antioxidant capacity (TAC; P = .003). On the 24th week, compared to placebo, CoQ10 supplementation further lowered blood pressure and TAC, reduced Triglyceride (P = .020) and low-density lipoprotein cholesterol (P = .016), and increased ApoA-I (P < .001) while decreasing homeostasis model assessment of insulin resistance index (P = .009). Adjustment for change of physical activity and energy intake did not alter the effect of CoQ10 on the aforementioned parameters but led to significant decrease of non–high-density lipoprotein cholesterol in CoQ10 group compared to placebo (P = .031).
Conclusions
Twenty-four-week treatment of CoQ10 ameliorates multiple CVD risk factors. The versatility and safety of CoQ10 makes it a potential candidate for the primary prevention of CVD.
Problem statement: Hyperlipidemia is well known to play a main role in the development of atherosclerosis. It is characterized by abnormally elevated cholesterol, Triglyceride, low density lipoprotein cholesterol and very low density lipoprotein cholesterol levels in the blood. It has been recognized for many years that hypercholesterolemia is a major risk factor for cardiovascular diseases such as atherosclerosis, myocardial infraction, heart attacks and cerebrovascular diseases. In recent years, Coenzyme Q10 has gained considerable attention as a dietary supplement capable of influencing cellular bioenergetics and as a supplementary treatment for some chronic diseases. Approach: The present study was undertaken to evaluate whether Coenzyme Q10 supplementation would alter high cholesterol diet-induced hypercholesterolemic model in female rats. Sixty female albino rats of the Wistar strain weighing between 34.3 and 42.1 g were used. The experimental animals were divided into six groups. Rats of group 1 served as controls, fed with standard diet and had free access to water for three months. Rats of group 2 were daily supplemented with 1 mL of corn oil containing 10 mg of cholesterol/rat for two months. Animals of group 3 were daily supplemented with 1 mL of corn oil containing 10 mg of cholesterol/rat for two months and daily supplemented with 1 mg Coenzyme Q10/rat at third month. Rats of group 4 were daily supplemented with 1 mL of corn oil /rat for two months. The experimental rats of group 5 were daily supplemented with 1 mL of corn oil /rat for two months and daily supplemented with 1 mg Coenzyme Q10/rat at third month. Rats of group 6 were supplemented with 1 mg Coenzyme Q10/rat at third month. The body weight percentage changes were determined after second and third months in all experimental groups. Results: After 2 months, the maximum changes of body weight were noted in groups treated with high cholesterol diet and corn oil. After three months, the maximum percentage changes were observed in groups two and four and the minimum changes were noted in sixth group supplemented with only Coenzyme Q10 at last period. Serum Triglycerides, cholesterol, High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), Atehrogenic Index (AI) and HDL Cholesterol (HDL-C) ratio were assessed at the end of experimental period. Significant increases in the levels of Triglycerides, cholesterol, LDL-C VLDL-C were noted in rats supplemented with high cholesterol diet, while the level of HDL-C was significantly reduced. Similar observations were noted in rats treated with high cholesterol diet plus Coenzyme Q10. Statistically, the treatment of Coenzyme Q10 in rats subjected to high cholesterol diet showed a decrease in the change levels of these parameters. Also, the Atehrogenic Index (AI) value was significantly elevated in rats supplemented with high cholesterol diet compared with control value. Administration of Coenzyme Q10 for a period of one month to rats supplemented with high cholesterol diet significantly decreased the percentage change of the Atehrogenic Index (IA) value. HDL-C ratio value was significantly decreased in rats supplemented with high cholesterol diet compared with control value. Treatment with Coenzyme Q10 for a period of last month significantly decreased the percentage change of the HDL-C ratio value in rats fed with high cholesterol diet. Conclusion: The present results suggested that Coenzyme Q10 possesses hypolipidemic effects in rats supplemented with high cholesterol diet. Thus, use of Coenzyme Q10 may be useful in the treatment of cardiovascular diseases in which atherosclerosis plays a major role.
Coptis chinensis Franch.root extract
Hypoglycemic andhypocholesterolemiceffects of Coptis chinensis franch inflorescence
Hypocholesterolemic and hypoglycemic activities of Coptis chinensis franch inflorescence (Coptis inflorescence) were studied using animal models.serum total andLDLcholesterol of rats fed adiet containing 1%cholesterol and 0.5% cholic acid increased, as compared with those of rats fed a normaldiet. The level of total andLDLcholesterol were reduced markedly in a dose dependent manner, in rats given Coptis inflorescence extract orally at doses of 0.25, 0.5 g/kg.day for 4 weeks. In diabetic rats induced by alloxan, Coptis inflorescence extract showed a significant (p < 0.05)blood sugarlowering activity at all experimented doses (0.125, 0.25 and 0.5 g/kg.day). Thehighest reduction ofblood sugar was about 58% when the rats were given Coptis inflorescence extract orally at a dose of 0.5 g/kg.day for 3 weeks. The 100 g dried water extract of Coptis inflorescence contained 8.11 g total alkaloid, 3.34 g berberin, 1.08 g palmatine and 0.66 g jatrorrhizine, which had long been identified as active compounds in Coptis chinensis franch root (Coptis root). Thus, the results suggest that Coptis inflorescence would beeffective in the prevention and management of coronary artery disease byloweringserumcholesterol andblood sugar.
Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in Hamsters Fed High-Fat diet
Palmatine (PAL) is one of the main alkaloids in Coptis chinensis. The present aim was to investigate the hypolipidemic effect and mechanism of palmatine in hamsters fed with high-fat diet (HFD). PAL treatment decreased serum total cholesterol (TC), Triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, as well as increased fecal excretion of TC and total bile acids (TBA) in hyperlipidemic hamsters. Furthermore, PAL treatment up-regulated low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein expression and down-regulated apical sodium-dependent bile salt transporter (ASBT) mRNA and protein expression. These results demonstrated that PAL as a potential natural cholesterol lowering agent works by up-regulating LDLR and CYP7A1 mRNA and protein expression, down-regulating ASBT mRNA and protein expression, as well as enhancing fecal excretion of TC and TBA. The findings in our study suggest that palmatine could be a potential natural agent for treating hyperlipidemia.
The effect of the MeOH extract of Coptidis Rhizoma on cell survival and adipogenesis in 3T3-L1 adipocytes is shown in Fig. 1A–C. The cytotoxicity of the MeOH extract obtained from Coptidis Rhizoma was measured by MTT assay. As shown in Fig. 1A, the MeOH extract of Coptidis Rhizoma exerted no cytotoxic effect at concentrations up to 200 μg/mL. The inhibitory effect of the MeOH extract obtained from Coptidis Rhizoma on Triglyceride contents in differentiated adipocytes was analyzed (Fig. 1B). As demonstrated in Fig. 1B, pretreat- ment with different concentrations of the MeOH extract (0, 12.5, 25, and 50 μg/mL) from Coptidis Rhizoma inhibited cellular Triglyceride accumulation in a dose dependent manner. Increased lipid accumulation during differentiation of preadipocytes into adipocytes is a typical phenomenon that occurs in 3T3-L1 cells and is used as a marker of differentiation. Lipid accumulation in cells was quantified by directly measuring Triglyceride levels. Triglycerides of fully differentiated adipocytes were stained with Oil-Red O staining solution (Fig. 1C). In the absence of the MeOH extract, fully differentiated cells had several lipid droplets as evidenced by the absorbance value of Oil-Red O eluted solution at 500 nm. The absorbance value of eluted dye was significantly decreased in the presence of the MeOH extract in a dose-dependent manner.
Cordycepin
The results suggested that levels of serum total cholesterol (TC), Triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) increased markedly in the two animal models by feeding high-fat diet. Meanwhile, cordycepin reduced levels of serum TC, TG, LDL-C, VLDL-C as well as LDL-C/HDL-C (high density lipoprotein cholesterol) and TC/HDL-C ratios. In concert with these effects, an increase in lipoprotein lipase (LPL) and hepatic lipase (HL) activity afforded by cordycepin was considered to contribute to the regulation on lipid profiles. Furthermore, no toxicity of cordycepin was observed by intragastric administration at the maximal tolerant dose in ICR mice for 14 days. The exact lipid-lowering effect of cordycepin needs further investigation.
Cordyceps polysaccharide
Blood was collected from each hamster using heparinized capillary tubes and centrifugated to obtain plasma. Total cholesterol (TC) and Triglyceride (TG) levels and LPL activity in the post-heparin plasma were assayed, and the lipid profiles of the lipoproteins were evaluated via the previous method
Costus spicatus (Jacq.) Sw.
Atheroprotective Properties of Costus spicatus (Jacq.) Sw. in Female Rats
Background: Costus spicatus (Jacq.) Sw. is a medicinal species frequently prescribed for the treatment of cardiovascular diseases. This study aims to evaluate theeffects of this species against the development ofAtherosclerosis. Methods: First, an anatomical study of the C. spicatus leaves was performed. Then, the extract (ESCS) was obtained and submitted to phytochemical analysis. Female rats were treated with a single dose of ESCS (2000 mg/kg) to assess acute toxicity. Other groups of female rats received an atherogenicdiet for 60 days. After 30 days, the animals were treated orally with ESCS (30 and 300 mg/kg), rosuvastatin (5 mg/kg), or vehicle once daily for 30 days.serumlipidsoxidized low-density lipoprotein, soluble adhesion molecules, interleukins 1β and 6, and markers of renal and liver function were measured. Renal function,blood pressure, electrocardiography, and vascular reactivity were also evaluated. Arteries, heart, liver, and kidney were also collected to evaluate the tissue redox state and histopathological analysis. Results: Prolonged treatment with ESCS induces significanthypolipidemic and antioxidanteffects, that prevent endothelial dysfunction and modulated the local inflammatory process,reducing the evolution of the atherosclerotic disease. Conclusions: This study provides a scientific basis for the popular use of C. spicatus for the treatment ofAtherosclerosis.
The present study of antidiabetic effects of rhizome extracts of C. spicatus on STZ in diabetic rats was evaluated, important mechanism; underlying hyperglycemia in diabetes mellitus. Excess of glucose in blood leads diabetes. It reacts with haemoglobin and forms glycosylated. Therefore, the total haemoglobin level is decreased in STZ diabetic rats. Administration of C. spicatus ethanolic rhizome extract reversed the total haemoglobin levels in STZ diabetic rats. Our study we observed that haemoglobin level is lowered in diabetic treated rats. After twenty eight days treatment ethanolic rhizomes extract showed important reduction of blood glucose level. It showed effectively maintain blood glucose level in normal and STZ induced diabetic rats. Different group of animals were used; ethanolic extract of C. spicatus treated groups (200 and 300 mg/kg BW) another treated groups glibenclamide, used as standard, results in rats showed a significantly increased insulin level when compared with diabetagenic rats treated groups as well as in the group of glibenclamide.
In diabetic rats, the effects of hydrogen bonding, cyaniding-3-glucoside, and delphinidin-3-glucoside on the activity of α-amylase and α-glucosidase were compared using potential extraction powder (20). To defend the body against the harmful effects of reactive oxygen species (ROS), the antioxidant system functions as a complex network of enzymes and non-enzymatic molecules that work together (47). To evaluate the effects of hypoglycemia, etc., in diabetic rats, measurements of glucose, glutathione, Triglycerides, HDL, LDL, and other relevant biomarkers in their serum would be necessary (28, 40). Non- enzymatic glycation, also referred to as the Maillard reaction, is a process where sugar molecules bind to proteins, lipids, and nucleic acids without the involvement of enzymes. (14, 48). AGEs (Advanced Glycation Endproducts) are molecules that result from the binding of glucose to proteins or lipids in the body. It is believed that they contribute to the development of microvascular complications in diabetes, such as neuropathy, nephropathy, and retinopathy (30).
Crataegus pinnatifida Bge. var majorN.E.Br. fruit extract
Theeffects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review
Metabolic syndrome is described as a group of risk factors in which at least three unhealthy medical conditions, including obesity,highblood sugar, hypertension or dyslipidemia occur simultaneously in a patient. These conditions raise the risk for diabetes mellitus and cardiovascular diseases. Many recent studies have focused on herbal remedies and their pharmacologicaleffects on metabolic syndrome. Crataegus pinnatifida or Chinese hawthorn has been widely used in the treatment of hyperlipidemia and cardiovascular diseases. Its leaves, fruits and seeds have various active substances such as, flavonoids, triterpenic acids and sesquiterpenes, which through different mechanisms can be beneficial in metabolic syndrome. Flavonoids found in the leaves of hawthorn can significantly reduce atherosclerotic lesion areas, the fruit extracts contain two triterpenic acids (oleanolic acid and ursolic acid), that have the ability to inhibit the acyl-coA-cholesterol acyltransferase (ACAT) enzyme and as a result reduce very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL)cholesterol levels. Another example regards a sesquiterpene found in the seeds of C. pinnatifida, which exhibits the ability to inhibit platelet aggregation, thus showing antithrombotic activity. Various studies have shown that C. pinnatifida can have beneficialeffects on controlling and treatinghighblood sugar, dyslipidemia, obesity andAtherosclerosis. The aim of this review is tohighlight the interestingeffects of C. pinnatifida on metabolic syndrome.
Consumption of functional foods for managing plasmacholesterol level has gained acceptance globally. The hypocholesterolaemic and vascular protectiveeffects of the dried fruit of Crataegus pinnatifida, hawthorn (Shan Zha), were investigated in rats fed with normaldiet,highcholesteroldiet (HCD) or HCD plus Shan Zha 80% ethanolic extract treatment (30 or 100 mg/kg/day, p.o.) for 4 weeks. Shan Zha extract markedlyreversed the increased plasma totalcholesterol andhigh density lipoproteincholesterol induced by HCD with a dose-dependent improvement on the atherogenic index. It also demonstrated good hepatoprotective function byreducinglipid content in the liver. The blunted endothelium-mediated aortic relaxation in HCD-fed rats was restored byhigh dosage of Shan Zha extract treatment. The current results showed that Shan Zha extract could provide itscholesterolloweringeffect by up-regulating hepatic CYP7A1 mRNA expression which leads to enhanced bile acid biosynthesis. It is postulated that the hypocholesterolaemiceffect is the primary beneficialeffect given by Shan Zha extract; it then leads to other secondary beneficialeffects such as vascular protective and hepatoprotective functions. Thus, Shan Zha extract could provide an overall improvement on the hepatic and vascular systems that may be important in relieving hypercholesterolaemia-related complications.
The effects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review
Insulin resistance is a common underlying factor in the formation of several diseases like obesity, dyslipidemia, hypertension, type 2 diabetes, and coronary diseases (31). Studies show that insulin resistance can be a contributing factor for the development of non-alcoholic fatty liver disease (NAFLD) (32) which consists of a spectrum of problems starting from the deposition of Triglyceride (TG) in the liver and then steatohepatitis and finally to fibrosis and cirrhosis (33).
In a recent 2015 study, the anti-obesity effects of a combination of C. pinnatifida leaf and Citrus unshia peel extracts (HTO48) were explored. In-vivo studies were performed on male Sprague Dawley rats. The rats were divided into two groups of chow diet group –and high fat diet group (HFD). Results showed that 0.2% and 0.6% concentrations of HTO48 (for 12 weeks) were able to reduce serum total cholesterol (TC) by 14.4% and 16.3 % and Triglyceride (TG) serum levels by 33.7 % and 31.9% in HFD-fed rats compared to the HFD control group. It was also shown that HTO48 was able to significantly reduce the expression of sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthase (FAS) genes, which are lipogenic genes that were higher in the HFD groups compared to the rats receiving a normal chow diet. Adipogenesis is a process in which preadipocytes mature into adipocytes by the enlargement of intracellular lipid droplets (a process involved in the formation of obesity) (42). In the study, the effects of different doses of HTO48 were examined on 3T3 -L1 preadipocytes by observing the expression of genes related to adipogenesis (PPAR Gama, aP2 and LPL mRNA). It was shown that HTO48 was able to significantly reduce lipid droplet formation and TG accumulation, thus inhibiting 3T3 -L1 preadipocytes differentiation into mature adipocytes. HTO48 was also able to reduce the expression of adipogenic transcription genes [peroxisome proliferator-activated receptor alpha (PPARg) and C/EBPa mRNA] and stimulate glycerol release (promoting lipolysis) in 3T3 -L1 adipocytes.
A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20–60 years with body mass indexes between 25 and 30 kg/m2. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks , the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of Triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals.
Crocetin
Objective:
Inhibition oflipidmetabolism in breast cancer has been suggested as aneffective approach for cancer therapy. Saffron-derived crocetin (Crt) and crocin (Cro) with the known anticancer activity, have shownhypolipidemiceffect in diabetes andAtherosclerosis. Here, we investigated theeffect of Crt/Cro onlipid content in breast cancer.
Materials and Methods:
A multi-model approach involving in vivo, in vitro and in silico studies was applied. The 4T1-induced breast cancer in mice was used to investigate theeffect of Crt/Cro oncholesterol (Chl) and Triglyceride (TG) levels inserum and tumor tissues. The Chl/Triglyceride levels were also assessed in the cytosol of MDA-MB-231 and MCF-7 breast cancer cell lines 6, 12 and 24 hr after Crt/Cro treatment. The interaction between Crt/Cro and hydroxymethylglutaryl coenzyme A reductase (HMGCR) was also computed by docking analysis.
Results:
Crt reduced bothserum (p=0.003) and tumor (p=0.011) Chl and Triglyceride (p=0.001) levels in mice. Cro reduced Triglyceride levels in tumor (p=0.014) andserum (p=0.002) and Chl level in tumor (p=0.013) tissues. Crt reduced both Chl and Triglyceride in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Cro reduced both Chl and Triglyceride in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Crt binds to the active site of HMGCR withhigher affinity (ΔG0=-6.6 kcal/mol) than simvastatin (ΔG0 =-6.0 kcal/mol).
Conclusion:
Crt and Croeffectively decreased Chl/Triglyceride content in the sera of tumor bearing mice, in breast tumors and breast cancer cell lines. Crt showed ahigherhypolipidemic potential than Cro. In silico analysis indicated Crt binding in the HMGCR active site.
The pancreatic lipase inhibitors were isolated from the fructus of Gardenia jasminoides ELLIS, and their antihyperlipidemic activities were measured. Gardeniae fructus (GF) water extract inhibited pancreatic lipase activity. Crocetin and crocin were isolated from GF water extract as inhibitors of pancreatic lipase with an IC50 value of 2.1 and 2.6 mg/ml (triolein as a substrate). Crocin and crocetin significantly inhibited the increase of serum TG level in corn oil feeding-induced Triglyceridemic mice, as well as that of serum Triglyceride and total and LDL cholesterol levels in Triton WR-1339-induced hyperlipidemic mice. These compounds also showed hypolipidemic activity in hyperlipidemic mice induced by high cholesterol, high fat or high carbohydrate diets for 5 weeks. The results suggest that the hypolipidemic activity of GF and its component crocin may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, crocetin, can improve hyperlipidemia.
Crocin
effect of crocin on glycated human low-density lipoprotein: A protective and mechanistic approach
Human low-density lipoprotein (LDL) is known to have a role in coronary artery diseases when it undergoes modification due to hyperglycaemic conditions. Plant products like crocin play an essential role in protecting against oxidative stress and in the production of advanced glycation end-products (A.G.E.s). In this study, the anti-glycatingeffect of crocin was analyzed using various biochemical, spectroscopic, and in silico approaches. Glycation-mediated oxidative stress was confirmed by nitroblue tetrazolium, carbonyl content, andlipid peroxidation assays, and it was efficiently protected by crocin in a concentration-dependent manner. A.N.S. fluorescence, thioflavin T (ThT) assay, and electron microscopy confirmed that the structural changes inLDL during glycation lead to the formation of fibrillar aggregates, which can be minimized by crocin treatment. Moreover, secondary structural perturbations inLDL were observed using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), where crocin was found to prevent the loss of secondary structure in glycatedLDL. Spectroscopic studies like U.V. absorbance, fluorescence spectroscopy, CD, FTIR, and fluorescence resonance energy transfer (FRET) provided insights into the interaction mechanism betweenLDL and crocin. Molecular docking supports these results with ahighly negative binding energy of −10.3 kcal/mol, suggesting the formation of a stableLDL-crocin complex. Our study indicates that crocin may be a potent protective agent against coronary artery diseases by limiting the glycation ofLDL in people with such disorders.
The pancreatic lipaseInhibitors were isolated from the fructus of Gardenia jasminoides ELLIS, and their antihyperlipidemic activities were measured. Gardeniae fructus (GF) water extract inhibited pancreatic lipase activity. Crocetin and crocin were isolated from GF water extract asInhibitors of pancreatic lipase with an IC50 value of 2.1 and 2.6 mg/ml (triolein as a substrate). Crocin and crocetin significantly inhibited the increase ofserum Triglyceride level in corn oil feeding-induced Triglyceride mic mice, as well as that ofserum Triglyceride and total andLDLcholesterol levels in Triton WR-1339-induced hyperlipidemic mice. These compounds also showedhypolipidemic activity in hyperlipidemic mice induced byhighcholesterol,high fat orhigh carbohydratediets for 5 weeks. The results suggest that thehypolipidemic activity of GF and its component crocin may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, crocetin, can improve hyperlipidemia.
Mechanism of hypolipidemic effect of crocin in rats: Crocin inhibits pancreatic lipase
The hypolipidemic mechanism of crocin, an active ingredient in Gardenia jasminoides Ellis and Crocus sativus L, was examined in rats. In diet-induced hyperlipidemic rats, a 10-day treatment with crocin significantly reduced serum Triglyceride, total cholesterol, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol level in the daily dose range of 25 to 100 mg/kg. Results of the modified fat-loading method indicated that crocin inhibited the absorption of fat and cholesterol and this inhibition is closely related to the hydrolysis of fat. In addition, the modified fat-balance method demonstrated that crocin increased the fecal excretion of fat and cholesterol in rats, but had no influence on the elimination of bile acids. The results of the in situ loop method and enzyme assay indicated that crocin could not directly block the absorption of cholesterol from rat jejunum but could selectively inhibit the activity of pancreatic lipase as a competitive inhibitor. These findings suggest that crocin yielded its hypolipidemic effect by inhibiting pancreatic lipase, leading to the malabsorption of fat and cholesterol.
Cuphea carthagenensis
Abstract
Ethnopharmacological relevance
Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment ofAtherosclerosis and circulatory disorders, no study evaluating theseeffects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimentalAtherosclerosis model using New Zealand (NZ) rabbits undergoingcholesterol-richdiet (CRD).
Material and methods
Dyslipidemia and atherogenesis were induced by administration of standard commercialdiet increased of 1%cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100 mg/kg, once daily for four weeks, starting from the 4th week of CRDdiet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks.serum levels of Triglyceride (TG), totalcholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined.
Results
CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase inlipid peroxidation and a reduction of hepatic glutathione andserum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC,LDL-C, VLDL-C levels and Triglycerides and promoted an increase in HDL-C levels in NZ rabbits. Theseeffects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment.
Conclusions
This study demonstrated that ES-CC reducesserumlipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-inducedAtherosclerosis.
Ethnopharmacological relevance
Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD).
Material and methods
Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100 mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. Serum levels of Triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined.
Results
CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and Triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment.
Conclusions
This study demonstrated that ES-CC reduces serum lipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-induced atherosclerosis.
Curcuma longa L. extract
It is generally accepted that free-radical inducedbloodlipid peroxidation and especially peroxidizedLDL play a central role in the pathogenesis ofAtherosclerosis and related cardiovascular disease. Moreover, recent researchhighlights the key contribution ofapolipoprotein B (apo B) to atherogenesis as the main inductor of one of its earlier steps, i.e. macrophage prolipheration. This has led us to investigate the apo B response to a veryeffective phenoliclipid-antioxidant, namely an hydroalcoholic extract of Curcuma longa, which according to our previous work does not show any toxiceffects and decreases the levels ofbloodlipid peroxides,oxidized lipoproteins and fibrinogen. The present study shows that a daily oral administration of the extract decreases significantly theLDL and apo B and increases the HDL and apo A of healthy subjects. This and recent data on the increased anti-atherogenic action of the physiological antioxidant tocopherol in the presence of phenolic co-antioxidants (which eliminate the tocopheroxyl radical), justifies planned clinical research to test the usefulness of the curcuma extract as a co-antioxidant complement to standard treatments to prevent or retardAtherosclerosis.
Background: Adipocytes accumulate triacylglycerol when excessive food consumption. Adipocyte dysfunction plays an important role in the obesity development. People with a body weight 40 % heavier than the average body weight population at risk of death two times greater than the average body weight. The use of anti-obesity drugs have many side effects, so it is necessary to find the anti-obesity drug with low toxicity. This ex vivo study was conducted to determine the activity of C. longa L. extract in inhibiting Triglycerides and cholesterol synthesis and lipid droplet formation on HepG2 cells compared to curcumin.
Methods: Anti-obesity activity includes reduced formation of lipid droplet in HepG2 cells can be observed using oil red O staining method. The measurement of Triglyceride level was performed according to Randox protocol using Randox TR 210 assay kit. Lipolytic activity by measuring cholesterol levels was performed based on Randox CH 200 kits.
Results: This study suggested that the extract of C. longa L. and curcumin have potential anti-obesity compounds. C. longa L. extract have higher activity in inhibiting Triglycerides and cholesterol synthesis compared to curcumin with inhibition activities 70.43% and 66.38% respectively in the highest concentration.
Conclusion: The C. longa extract posses the anti-adipogenesis potential on inhibiting the synthesis of Triglycerides and cholesterol and lipid droplet formation in HepG2 cell as anti-obesity parameters better than curcumin.
Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world’s adult population is about 20%–25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitro, in vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects.
Curcumin
Atherosclerosis is a major cause of cardiovascular disease caused byhighcholesterol. Reduced intestinalcholesterolabsorption has been shown to exert strongcholesterol-lowering and antiatherogeniceffects. Previously, we reported that curcumin reducedcholesterolabsorption inhigh-fatdiet–fed hamster by downregulating the intestinal expression of Niemann-Pick C1-like 1. Here, we tested the hypothesis that supplementation with curcumin can also reduce intestinalcholesterolabsorption inhigh-fatdiet–fedapolipoprotein E knockout (ApoE−/−) mice and preventAtherosclerosis development. ApoE−/− mice were fed ahigh-fatdiet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Aortic sinus sections revealed that curcumin supplementation reduced the extent of atherosclerotic lesions by 45%. Curcumin treatment also reducedcholesterol accumulation in the aortas by 56% and lowered plasma totalcholesterol and low-density lipoproteincholesterol levels. Moreover, the antiatherogenic andcholesterol-lowering effects of curcumin coincided with a significant decrease in intestinalcholesterolabsorption. It was reduced by nearly 51%, and the decreasedcholesterolabsorption was modulated by inhibiting the intestinal expression of Niemann-Pick C1-like 1, predominantly in the duodenal and jejunal segments of the small intestine. These findings support the hypothesis that curcumin supplementation reduces intestinalcholesterolabsorption and preventsAtherosclerosis inhigh-fatdiet–fed ApoE−/− mice. Curcumin affords a potent antiatherogenic action by inhibiting intestinalcholesterolabsorption in the mouse.
Regulation ofPCSK9 by nutraceuticals
PCSK9, a criticalInhibitor ofLDLR, is up-regulated by both HNF1α and SREBP-2 transcription factors. Besides
PCSK9, SREBP-2 up-regulatesLDLR gene. Nutraceuticals, including curcumin and berberine, can decrease plasma
LDL-C levels through elevation of the hepaticLDLR via inhibiting HNF1α which is a specific transcription factor
forPCSK9 gene. Statins increase the expression of bothPCSK9 andLDLR through the activation of SREBP-2,
resulting inPCSK9-mediated attenuation of theireffects
Background
dietary phytosterols (PS) are well-known hypocholesterolaemic agents. Curcumin elicits hypolipidaemic and anti-inflammatoryeffects in preclinical studies, however, consistent findings in humans are lacking.
Objective
Concurrent PS and curcumin supplementation may exhibit enhanced hypocholesterolaemic and anti-inflammatoryeffects to optimise cardio-protection. The objective of this trial was to investigate theeffects ofdietary intervention with PS with or without curcumin onbloodlipids (primary outcome) in hypercholesterolaemic individuals.
Methods
A double-blinded, randomised, placebo-controlled, 2 × 2 factorial trial was conducted in hypercholesterolaemic individuals. Participants received either placebo (PL, no phytosterols or curcumin), phytosterols (PS, 2 g/d), curcumin (CC, 200 mg/d) or a combination of PS and curcumin (PS-CC, 2 g/d–200 mg/d respectively) for four weeks. Primary outcomes included fasting totalcholesterol (TC),LDL-cholesterol, HDL-cholesterol, Triglycerides (TG), TC-to-HDL-C ratio (TC:HDL-C). Secondary outcomes included anthropometrics and fastingbloodglucose concentrations.
Results
Seventy participants with a mean (±SEM) fasting TC concentration of 6.57 ± 0.13 mmol/L completed the study (PL, n = 18; PS, n = 17; CC, n = 18; PS-CC, n = 17). PS and PS-CC supplementation significantly lowered TC,LDL-cholesterol and TC:HDL-C post-intervention (p < 0.05). Reductions from baseline in the PS group were 4.8% and 8.1% for TC andLDL-cholesterol respectively (p < 0.05). CC exhibited non-significant reduction (2.3% and 2.6%) in TC andLDL-C respectively, however, the PS-CC resulted in a greater reduction in TC (11.0%) andLDL-cholesterol (14.4%) than either of the treatments alone (p < 0.0001). The reduction in the PS-CC treatment was significantly greater compared to those for CC (p < 0.05) or PL (p < 0.01) alone. Plasma HDL-cholesterol and Triglyceride concentrations remained unchanged across all groups. No adverse sideeffects were reported.
Conclusions
The addition of curcumin to phytosterol therapy provides a complementarycholesterol-loweringeffect that is larger than phytosterol therapy alone. Implications of these findings include the development of a single functional food containing both the active ingredients for enhancedlipid-lowering and compliance in hypercholesterolaemic individuals.
Background
Dyslipidemia is an important and common cardiovascular risk factor in the general population. The lipid-lowering effects of turmeric and curcumin are unconfirmed. We performed a meta-analysis to assess the efficacy and safety of turmeric and curcumin in lowering blood lipids in patients at risk of cardiovascular disease (CVD).
Methods
A comprehensive literature search was conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to identify randomized controlled trials (published as of November 2016) that assessed the effect of turmeric and curcumin on blood lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and Triglycerides (TG). Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effect.
Results
The analysis included 7 eligible studies (649 patients). Turmeric and curcumin significantly reduced serum LDL-C (SMD = −0.340, 95% confidence interval [CI]: −0.530 to −0.150, P < 0.0001) and TG (SMD = −0.214, 95% CI: −0.369 to −0.059, P = 0.007) levels as compared to those in the control group. These may be effective in lowering serum TC levels in patients with metabolic syndrome (MetS, SMD = −0.934, 95% CI: −1.289 to −0.579, P < 0.0001), and turmeric extract could possibly have a greater effect on reducing serum TC levels (SMD = −0.584, 95% CI: −0.980 to −0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies.
Conclusions
Turmeric and curcumin may protect patients at risk of CVD through improving serum lipid levels. Curcumin may be used as a well-tolerated dietary adjunct to conventional drugs. Further research is required to resolve uncertainties related to dosage form, dose and medication frequency of curcumin.
Human studies of curcumin extract on lipid-lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty-five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high-density lipoprotein cholesterol (HDL-C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p < 0.05), and the level of low-density lipoprotein cholesterol (LDL) was significantly reduced (120.55 ± 36.81 to 106.51 ± 25.02 mg/dL, p < 0.05). The Triglyceride-lowering effect, a reduction of 65 mg/dL, was also found in this study. In subgroups analysis, the consumption of curcumin may have a lowering cholesterol effect in male patients and an increasing HDL-C effect in female patients, both of which result in a decrease of T-Chol/HDL-C ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was associated with lipid-lowering effect but did not improve weight and glucose homeostasis in the patients with metabolic syndrome. Daily curcumin consumption may be an alternative choice to modify cholesterol-related parameters, especially in metabolic syndrome patients.
Scope: Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Stains are widely prescribed to lower cholesterol levels, but natural dietary compounds may also be effective. Therefore, we studied the effect of the natural dietary compound curcumin on atherosclerosis and its underlying mechanisms based on plasma and hepatic lipid metabolism.
Methods and results: LDLR(-/-) mice were fed a high-cholesterol diet and treated with curcumin, lovastatin or control (n=10 per group) for 18 wk. Aortic arch sections revealed curcumin ameliorated early atherosclerotic lesions, lipid infiltration, ICAM-1 and VCAM-1 localization, similar to lovastatin treatment. Furthermore, curcumin lowered plasma cholesterol, Triglycerides, LDL cholesterol and Apo B levels as well as CETP activity, while curcumin increased plasma HDL cholesterol and liver Apo A-I expression, similar to lovastatin treatment. Curcumin caused transcriptional inhibition of HMG-CoA reductase, independent of ACAT1 and ACAT2 expression. Hepatic PPARα and LXRα expression was upregulated by curcumin treatment. Hepatic complement factor D (Cfd) and systemic CRP levels, markers of immune complement pathway activation, were significantly reduced by curcumin treatment.
Conclusion: Long-term curcumin treatment lowers plasma and hepatic cholesterol and suppresses early atherosclerotic lesions comparable to the protective effects of lovastatin. The anti-atherogenic effect of curcumin is mediated via multiple mechanisms including altered lipid, cholesterol and immune gene expression.
Molecular mechanisms of hypolipidemic effects of curcumin
Recent evidence suggests potential benefits from phytochemicals and micronutrients in reducing the elevated oxidative and lipid-mediated stress associated with inflammation, obesity, and atherosclerosis. These compounds may either directly scavenge reactive oxygen or nitrogen species or they may modulate the activity of signal transduction enzymes leading to changes in the expression of antioxidant genes. Alternatively, they may reduce plasma lipid levels by modulating lipid metabolic genes in tissues and thus reduce indirectly lipid-mediated oxidative and endoplasmic reticulum stress through their hypolipidemic effect. Here we review the proposed molecular mechanisms by which curcumin, a polyphenol present in the rhizomes of turmeric (Curcuma longa) spice, influences oxidative and lipid-mediated stress in the vascular system. At the molecular level, mounting experimental evidence suggests that curcumin may act chemically as scavenger of free radicals and/or influences signal transduction (e.g., Akt, AMPK) and modulates the activity of specific transcription factors (e.g., FOXO1/3a, NRF2, SREBP1/2, CREB, CREBH, PPARγ, and LXRα) that regulate the expression of genes involved in free radicals scavenging (e.g., catalase, MnSOD, and heme oxygenase-1) and lipid homeostasis (e.g., aP2/FABP4, CD36, HMG-CoA reductase, and carnitine palmitoyltransferase-I (CPT-1)). At the cellular level, curcumin may induce a mild oxidative and lipid-metabolic stress leading to an adaptive cellular stress response by hormetic stimulation of these cellular antioxidant defense systems and lipid metabolic enzymes. The resulting lower oxidative and lipid-mediated stress may not only explain the beneficial effects of curcumin on inflammation, cardiovascular, and neurodegenerative disease, but may also contribute to the increase in maximum life-span observed in animal models.
Curcumin is an herbal polyphenol extensively investigated for antioxidant, anti-inflammatory, and hypolipidaemic properties. In the present review, the efficacy of curcumin for improving a plasma lipid profile has been evaluated and compared with statins, a well-known class of medicines for treating hypercholesterolemia and hyperlipidaemia. Curcumin is presumably most effective in reducing Triglyceride (TG), while statins are most efficient in lowering low-density lipoproteins-cholesterol (LDL-C). Additionally, various molecular and metabolic mediators of cholesterol and plasma lipid homeostasis are discussed in relation to how they are modulated by curcumin or statins. Overall, curcumin influences the same mediators of plasma lipid alteration as statins do. Almost all the pathways through which cholesterol trafficking takes place are affected by these agents. These include gastrointestinal absorption of dietary cholesterol, hepatocellular removal of plasma cholesterol, the mediators of reverse cholesterol transport, and removal of cholesterol from peripheral tissues. Moreover, the reactive oxygen species (ROS) scavenging potential of curcumin limits the risk of lipid peroxidation that triggers inflammatory responses causing cardiovascular diseases (CVD) and atherosclerosis. Taken together, curcumin could be used as a safe and well-tolerated adjunct to statins to control hyperlipidaemia more effectively than statins alone.
Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat–fed hamsters
This study investigated the effect of curcumin (0.05-g/100-g diet) supplementation on a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) fed to hamsters, one of the rodent species that are most closely related to humans in lipid metabolism. Curcumin significantly lowered the levels of free fatty acid, total cholesterol, Triglyceride, and leptin and the homeostasis model assessment of insulin resistance index, whereas it elevated the levels of high-density lipoprotein cholesterol and apolipoprotein (apo) A-I and paraoxonase activity in plasma, compared with the control group. The levels of hepatic cholesterol and Triglyceride were also lower in the curcumin group than in the control group. In the liver, fatty acid β-oxidation activity was significantly higher in the curcumin group than in the control group, whereas fatty acid synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and acyl coenzyme A:cholesterol acyltransferase activities were significantly lower. Curcumin significantly lowered the lipid peroxide levels in the erythrocyte and liver compared with the control group. These results indicate that curcumin exhibits an obvious hypolipidemic effect by increasing plasma paraoxonase activity, ratios of high-density lipoprotein cholesterol to total cholesterol and of apo A-I to apo B, and hepatic fatty acid oxidation activity with simultaneous inhibition of hepatic fatty acid and cholesterol biosynthesis in high-fat–fed hamsters.
Cyclocarya paliurus
Results
Different Cyclocarya paliurus polar extracts, especially ChE reduced the levels of serum total cholesterol (TC), Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and hepatic TC and TG, enhanced the level of serum high-density lipoprotein cholesterol (HDL-C), restored hepatic and renal function indices and histomorphology. HMG-CoA reductase activity and mRNA expression were decreased, while CYP7A1 activity and mRNA expression as well as the level of fecal and hepatic bile acid were increased by ChE. LC–MS analysis of ChE revealed the presence of six main triterpenoids, which might be responsible for its antihyperlipidemic bioactivity.
Cyclocarya paliurus prevents high fat diet induced hyperlipidemia and obesity in Sprague–Dawley rats
Cyclocarya paliurus (CP; qing qian liu), which is used as an herbal tea in China, has been confirmed to have therapeutic effects on hyperlipidemia and obesity, and therefore it is widely consumed to prevent metabolic diseases such as hyperlipidemia and diabetes. In this study, we investigated the preventive effects of CP on obesity and hyperlipidemia, as well as the underlying mechanisms involved in intestinal secretion of apolipoprotein (apo) B48. Sprague–Dawley rats were fed a high-fat diet (HFD) and with or without various concentrations of an ethanol extract of CP (CPE; 2, 4, or 8 g·(kg body mass)–1) administered by gavage for 8 weeks. From the results we see that CPE dose-dependently blocked increases in body mass, and decreased food utilization as well as visceral fat mass. Decreased serum levels of total cholesterol, Triglycerides, and low density lipoprotein cholesterol, and elevated levels of high density lipoprotein cholesterol, as well as lowered levels of total cholesterol and Triglycerides in the liver were also noticed in CPE-treated rats. Magnetic resonance images indicated that the abnormal fat storage induced by the HFD was obviously suppressed by CPE. In addition, ELISA analysis showed reduced fasting serum apoB48 in the CPE treatment groups. Based on the above results, CPE shows a promising preventive effect on obesity and hyperlipidemia, partially through suppressing intestinal apoB48 overproduction.
Cymodocea nodosa
This study aims to evaluate for the first time theeffects of Cymodocea nodosa sulphated polysaccharide (CNSP) on lipase activity in vitro and in vivo tohigh fatdiet (HFD)-rats on body weight,lipid profile and liver-kidney functions. The administration of CNSP decreases the body weight and inhibits lipase activity of obese rats inserum and intestine as compared with untreated HDF-rats. This decrease in lipase activity leads tolipid regulation shown by the decrease of totalcholesterol (T-Ch), Triglycerides (TG) and low density lipoproteincholesterol (LDL-C) and an increase inhigh density lipoproteincholesterol (HDL-C) levels in HFD-rats. Additionally, CNSP administration to HFD-rats induces anti-oxidant activity observed by the increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels and protects liver-kidney functions proven by a decrease in the levels of toxicity parameters inblood.
This study aims to evaluate for the first time the effects of Cymodocea nodosa sulphated polysaccharide (CNSP) on lipase activity in vitro and in vivo to high fat diet (HFD)-rats on body weight, lipid profile and liver-kidney functions. The administration of CNSP decreases the body weight and inhibits lipase activity of obese rats in serum and intestine as compared with untreated HDF-rats. This decrease in lipase activity leads to lipid regulation shown by the decrease of total cholesterol (T-Ch), Triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) and an increase in high density lipoprotein cholesterol (HDL-C) levels in HFD-rats. Additionally, CNSP administration to HFD-rats induces anti-oxidant activity observed by the increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels and protects liver-kidney functions proven by a decrease in the levels of toxicity parameters in blood.
This new study aimed to evaluate for the first time the effect of Cymodocea nodosa extract (CNE) on α-amylase activity, hyperglycemia and diabetes complications in the alloxan-induced diabetic rats. The in vitro evaluation and oral administration of CNE to surviving diabetic rats inhibited key enzyme related to hyperglycemia as α-amylase, helped to protect the β cells of the rats from death and damage confirmed by oral glucose test tolerance (OGTT), which leads to decrease in blood glucose level by 49% as compared to untreated diabetic rats. The CNE also decreased the Triglyceride, low density lipoprotein (LDL) cholesterol and total cholesterol rates in the plasma of diabetic rats by 46%, 35%, and 21%, respectively, and increased the high density lipoprotein (HDL) cholesterol level by 36%, which helped maintain the homeostasis of blood lipid. When compared to those of the untreated diabetic rats, the superoxide dismutase, catalase, and glutathione peroxidase levels in the pancreas, liver and kidney of the rats treated with this supplement were also enhanced significantly. Moreover, a significant decrease was observed in the lipid peroxidation level in the tested organs of diabetic rats after CNE administration. This positive effect of CNE was confirmed by histological study. Overall, the findings presented in this study demonstrate that CNE has both a promising potential with a valuable hypoglycemic and hypolipidemic functions.
Cynara scolymus L.leaves extract
hypolipidemic and antiatherogeniceffects of Cynara scolymus incholesterol-fed rats
Cynara scolymus L., Asteraceae, are traditionally used to treat dyspepsia. This study evaluated thehypolipidemic and antiatherogeniceffects of an aqueous extract prepared from the leaves of C. scolymus in rat’s model. hypercholesterolemic rats (1%cholesterol and 0.5% cholic acid for 15 days) were treated (0.5 ml/200 g) with extract of C. scolymus (150, 300, or 600 mg/kg p.o.; n = 6) or simvastatin (4 mg/kg p.o.; n = 6) once per day for 30 days along with hypercaloricdiet. A control group (C) was given water (0.5 ml/200 g; n = 6). Ahigh-cholesteroldiet was maintained throughout the treatment period. Rats treated with extract of C. scolymus (150, 300, or 600 mg/kg) and simvastatin showed significant decreases inserum levels of totalcholesterol (−46.9%, −51.9%, −44%, and −41.9%, respectively) and low-density lipoprotein-cholesterol (LDL-C; −52.1%, −54.8%, −51.9%, and −46.7%, respectively), compared with group C (p < 0.005). Biochemical analyses revealed significant decrease in the concentration of IL-1, IL-6, TNF-α, IFN-γ, C-reactive protein,oxidized-LDL, and antioxidized-LDL in rats treated with extract of C. scolymus (150, 300, or 600 mg/kg). There were no differences inserum ALT enzyme activity between the groups. Our results suggest thathypolipidemic and antiatherogeniceffects could be related with the presence of polar substances present in aqueous extract of C. scolymus.
Cynara scolymus (artichoke) and its efficacy in management of obesity
Obesity, the most prevalent metabolic disorder is associated with elevated body fat mass and body mass index. Cynara scolymus L. is famous for its hepatoprotective properties, also it seems to have good potency as anti-obese agent. In this review article, the potency of C. scolymus as anti-obese agent has been evaluated. The evidences based information were extracted from accessible international electronic databases (PubMed, Springer, Science Direct, Wiley and Google), and books (Persian or English), by key word of Cynara scolymus and artichoke plus obesity or the mechanism of anti-obese drugs. C. scolymus inhibits the digestive enzymes such as pancreas lipase, α-amylase, α-glucosidase, increases the bile secretion, inhibits of inflammation and ROS, improves liver function, gut microbiota, enhances lipolysis and lipid metabolism, and reduces blood glucose in preclinical and clinical studies. Designing large multi-center clinical trials on C. scolymus and evaluating its effects on weight loss in comparison with famous drug such as orlistate could be the subject of future studies.
Obesity plays a pivotal role in the insulin resistance disease, which is related to hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. The purpose of the present study was done to evaluate the effect of artichoke leaves extract (ALE) in the high-fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. Body and organ weights, serum lipid profile, cardiac markers, and antioxidants enzymes were measured. Oral administration of ALE at two doses 200 and 400 mg/kg for a period of 60 days showed a significant decrease in body and organ weights, serum total cholesterol, Triglycerides, LDH, ALT accompanied by decreasing in oxidative stress biomarker (MDA, and AOPP) and increasing antioxidant enzymes (SOD, CAT, and GPx) levels as compared to HFD groups. The histological findings showed a cardioprotective effect of ALE. These findings suggest that ALE exert anti-oxidant cardiac effects in HFD- induced obese rats.
The aim of this study was to assess the effect of artichoke (Cynara scolymus) leaf aqueous extract (ALE) on streptozotocin (STZ)-induced diabetic rats. ALE (200 and 400 mg/kg body weight) was administered to STZ-induced diabetic rats and fasting blood glucose, total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), atherogenic index, lipid peroxidation (LPO), red blood cell (RBC) superoxide dismutase (SOD) activity and plasma antioxidant capacity were measured. The oral administration of ALE for 21 days significantly reduced TC, TG, LDL-C, VLDL-C and hyperglycemia in treated diabetic rats as compared to diabetic control group. ALE also markedly ameliorated the level of plasma malondialdehyde (MDA) and increased plasma antioxidant capacity of treated diabetic group. The results clearly indicate the beneficial reducing effects of ALE on serum TC, TG, LDL-C, VLDL-C, glucose levels and plasma MDA level in STZ-treated rats.
Investigation of the Effect of Artichoke (Cynara Scolymus L.) on Characteristics of the Fatty Liver
On the other hand, lowering blood sugar, Triglyceride, and cholesterol levels showed the positive effects of this plant in reducing and improving liver function and treatment of hyperlipidemia [35]. Studies have shown that this plant reduces lipids and lipoproteins by interfering with the biosynthesis of cholesterol and also affects the production and secretion of bile in the liver. They have also indicated that this plant reduces lipids and lipoproteins by interfering with the biosynthesis of cholesterol and also affects the production and secretion of bile in the liver. It seems that the existence of flavonoid compounds in this plant is responsible for its effects, especially in improving liver’s function [40, 41].
Most of medications do not decrease TG levels, however, our results showed that C. dactylon not only reduces the lipid levels but also lowers the plasma level of TG.
Cynarin
Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or Triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.
Cynodon dactylon extract
Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study,Anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normaldiet, sham group received ahighcholesteroldiet (HCD; 1.50%cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg-1), moderate (200 mg kg-1) and maximum (400 mg kg-1) doses via gavages. The last group received atorvastatin (10 mg kg-1) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including totalcholesterol (TC), Triglyceride (TG), low-density lipoproteincholesterol (LDL-C) andhigh-density lipoproteincholesterol (HDL-C) were assessed in theblood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon-treated groups. Treatment of HCD animals with C. dactylon positively changedlipid profile bylowering of TC, Triglyceride andLDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.
Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg-1), moderate (200 mg kg-1) and maximum (400 mg kg-1) doses via gavages. The last group received atorvastatin (10 mg kg-1) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon-treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.
A Review of the Pharmacological and Nutraceutical Properties of Cynodon dactylon
Simultaneous administration of C dactylon extract caused a significant decrease in serum TC, LDL-c, and VLDL-c, suggesting a beneficial modulatory influence on cholesterol metabolism and turnover. The reduction in the ratio of TC:HDL-c observed in the extract-treated rats might be a consequence of a higher proportion of HDL-c, which could be due to increased reverse cholesterol transport from peripheral organs to the liver.33, 34 Elevated serum TG is considered an independent risk factor for CVD.35 TG accumulation caused by dietary cholesterol may contribute to the reduction of fatty acid beta-oxidation and the preference of cholesterol ester to afflux to LDL during the onset of biosynthesis and secretion of LDL.36, 37 A significant decline in the serum TG concentration observed in extract-treated rats supports the cardiovascular protective influence. The mechanism by which C dactylon extract lowered the serum TG concentration could be either by decreasing VLDL synthesis, by channeling VLDL through pathways other than to LDL, or an increase in lipoprotein lipase activity.
Antihyperlipedemic activity of Cynodon dactylon extract in high-cholesterol diet fed Wistar rats
The aim of the present study was to investigate the potential role of an ethanolic extract of the entire plant of Cynodon dactylon in lowering the plasma lipid parameters in rats fed a high cholesterol diet. Wistar albino rats were randomly divided into four groups of six and for 45 days were administered either: 0.5 ml water (negative controls); 30 mg cholesterol (hypercholesterolemic animals); C dactylon extract at 400 mg/kg body weight (positive control); or the same doses of both cholesterol and the extract (test animals). The effects of C dactylon on the lipid profile were assessed by measuring the plasma concentrations of total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and very low-density lipoprotein cholesterol (VLDL-c). Administration of cholesterol showed significant elevation (p < 0.001) of TC, LDL-c, VLDL-c, and TG concentrations, and of the TC:HDL-c ratio (p < 0.05). Concurrent administration of C dactylon extract caused a significant decrease (p < 0.001) in the concentrations of serum TC, LDL, HDL, VLDL TGs when compared with cholesterol fed control rats. The TC:HDL-c ratio was also declined significantly (p < 0.001). These results suggest lipid-lowering effects of C dactylon, which serves as a new potential natural product for preventing hyperlipidemia.
d-Allulose
d-Allulose, a C-3 epimer of d-fructose, is a rare sugar reported to be a non-caloric sweetener having several health beneficialeffects including anti-hyperglycemia and anti-obesity. However, the impact ofdietary d-allulose oncholesterolmetabolism remains unclear. Therefore, we studied theeffects of d-allulose on thecholesterolmetabolism of Golden Syrian hamsters, an animal model with alipidmetabolism similar to that of humans. Hamsters received either normaldiet (ND) orhigh-fatdiet (HFD) with or without 3% d-allulose for 4 or 8 weeks. While there were no significant differences in totalserumcholesterol levels between the groups, d-allulose significantly increased HDL-cholesterol levels in ND-fed hamsters and decreasedLDL-cholesterol levels in HFD-fed hamsters, causing an overall decrease in theLDL/HDL ratio. Furthermore,dietary d-allulose decreasedserum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in bothdiets. In conclusion, d-allulose may favorably modulatecholesterolmetabolism byreducingPCSK9 in hamsters.
d-Glucaric acid
The beneficial properties of different vitamins, minerals, and other micronutrients have been studied for quite some time. But only recently has the potential usefulness of d-glucaric acid and its derivatives in disease prevention been demonstrated. d-Glucaric acid is an end product of the d-glucuronic acid pathway in mammals. Itsdietary sources include different fruits and vegetables. In the present study, d-glucaric acid content in various fruits and vegetables was found to range from about 0.1 g/kg in grapes and lettuce to about 3.5 g/kg in apples and broccoli. It was also shown that purifieddiets containing calcium d-glucarate or potassium hydrogen d-glucarate markedly loweredserum levels ofcholesterol in female Sprague-Dawley rats. The d-glucarates reduced totalserumcholesterol in rats by up to 14% (P<0.05) and loweredLDL-cholesterol by up to 35% (P<0.05), but had noeffect on HDLcholesterol. These results provide a starting point for further studies of the mechanism by which d-glucaric acid salts lowerserumcholesterol.
Dendropanax morbifera
Antiobesity andcholesterol–lowering effects of Dendropanax morbifera Water Extracts in Mouse 3T3-L1 Cells
Obesity is the most common metabolic disease in developed countries and has become a global epidemic in recent years. Obesity is associated with various metabolic abnormalities, includingglucose intolerance, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Leaves from the plant Dendropanax morbiferus are beneficial to health as they containhigh levels of vitamin C and tannin. There have been seminal studies on the anticancer, antimicrobial, antidiabetes, and antihyperglycemiceffects of treatments with D. morbiferus trees. Herein, we investigated the toxicity of D. morbiferus water (DLW) extracts in vitro, and demonstrated no toxicity at 5–500 μg/mL in 24–72-h experiments with 3T3-L1 cells. The DLW increased cell viability at 48 h and inhibited adipogenesis in 3T3-L1 cells byreducing intracellular Triglyceride levels andglucose uptake. In addition, mRNA and protein expression levels of adipogenesis-related genes were lowered by DLW, suggesting antiobesityeffects in mouse 3T3-L1 cells. Because few studies have demonstratedcholesterol-lowering effects of D. morbiferus, we investigated the activities of adipogenic transcriptional factors following treatments of 3T3-L1 cells with D. morbiferus and observed increased CEBPα, CEBPβ, PPARγ, and SREBP1 activities in the cells, indicating that DLW extracts inhibit adipogenesis.
Obesity is the most common metabolic disease in developed countries and has become a global epidemic in recent years. Obesity is associated with various metabolic abnormalities, including glucose intolerance, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Leaves from the plant Dendropanax morbiferus are beneficial to health as they contain high levels of vitamin C and tannin. There have been seminal studies on the anticancer, antimicrobial, antidiabetes, and antihyperglycemic effects of treatments with D. morbiferus trees. Herein, we investigated the toxicity of D. morbiferus water (DLW) extracts in vitro, and demonstrated no toxicity at 5–500 μg/mL in 24–72-h experiments with 3T3-L1 cells. The DLW increased cell viability at 48 h and inhibited adipogenesis in 3T3-L1 cells by reducing intracellular Triglyceride levels and glucose uptake. In addition, mRNA and protein expression levels of adipogenesis-related genes were lowered by DLW, suggesting antiobesity effects in mouse 3T3-L1 cells. Because few studies have demonstrated cholesterol-lowering effects of D. morbiferus, we investigated the activities of adipogenic transcriptional factors following treatments of 3T3-L1 cells with D. morbiferus and observed increased CEBPα, CEBPβ, PPARγ, and SREBP1 activities in the cells, indicating that DLW extracts inhibit adipogenesis.
D. morbifera reduces bad cholesterol and Triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice.
The purpose of this study was to determine the effects of dried Dendropanax morbifera leaf extracts on lipid profiles of mice fed a high-fat and -cholesterol diet (HFCD). ICR mice were divided into six groups based on mice fed AIN-93G diet (Normal), HFCD (Control), HFCD+100 mg/kg/d of D. morbifera leaf aqueous extract (DA-100), HFCD+200 mg/kg/d of D. morbifera leaf aqueous extract (DA-200), HFCD+100 mg/kg/d of D. morbifera leaf ethanol extract (DE-100), or HFCD+200 mg/kg/d of D. morbifera leaf ethanol extract (DE-200) for 7 weeks. The final body weights of mice fed D. morbifera extracts were all lower than those of the control group. Mice treated with D. morbifera extracts showed significantly reduced plasma and hepatic Triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol levels, along with increased plasma high-density lipoprotein cholesterol level. Fecal TG level was higher in DE-100 and DE-200 groups and TC level was significantly higher in the DA-200 and DE-200 groups. Relative liver weight, spleen weight, and testicle fat weight in mice treated with D. morbifera were reduced compared to the control group. Plasma insulin, aspartate transaminase, and alanine transaminase levels of experimental groups were also lower than those of the control group. All mice treated with D. morbifera extracts had lower malondialdehyde (MDA) content and higher superoxide dismutase (SOD) activity than the control group. Particularly MDA levels of the DA-200 and DE-200 groups and SOD levels of the DE-200 group were identical to levels of the normal group. These results suggest that D. morbifera extracts have lipid improvement effects in mice fed a HFCD.
Dioscorea zingiberensis
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Dioscoreaceae (Dioscorea nipponica Makino)
Naturally OccurringPCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Diosgenin
The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review
Hyperlipidemia is a pathological disorder of lipid metabolism that has various causes. The clinical manifestations of hyperlipidemia include increased serum cholesterol, Triglycerides, and low-density lipoprotein cholesterol (LDL-C), and decreased serum high-density lipoprotein cholesterol (HDL-C). Imbalance of LDL-C and HDL-C can increase the risk of cardiovascular (CV) events, including myocardial infarction and stroke.1 Data released by the American Heart Association in 2018 showed that CV disease (CVD) is the most lethal disease worldwide.2 According to the 2010 global burden of disease study, 15.6 million people died of CVD, accounting for 29.6% of all deaths.3 Hyperlipidemia has a long disease course, and many underlying causes, reflecting its complex etiology.4 Dyslipidemia is a significant risk factor for coronary artery disease and stroke; hence, prevention and appropriate management of dyslipidemia can markedly lower the related morbidity and mortality.5
Diospyros kaki Thunb. extracts
cholesterol-loweringeffect of astringent persimmon fruits (Diospyros kaki Thunb.) extracts
This study aimed to investigate theeffects of ethanol extract of astringent persimmon on antioxidant activity,cholesterol, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity, and mRNA expression ofcholesterolmetabolism-related genes in human hepatoma cell line (HepG2 cells). In the results, DPPH and ABTS radical scavenging activity showed that the different types cultivars of astringent persimmon was similar to Vitamin C as positive control. However, there are not significant differences among samples. In addition, our results showed thatcholesterol amounts and HMG-CoA reductase activity were inhibited by astringent persimmon in HepG2 cells. Further, treatment with astringent persimmon upregulated the expression ofLDL receptor and SREBP-2, and also increased the level of HDL-associated ABCA1. Taken together, our results indicate that astringent persimmon regulatecholesterol accumulation by inhibiting the oxidative stress and controlling the levels ofLDL & HDLassociated gene.
This study aimed to investigate the potential of freeze-dried persimmon powder (Diospyros kaki Thumb.) to protect against dyslipidemia induced by a high-fat/cholesterol diet (HFD) in a rat model. Methods: Fifty Wistar rats were randomly divided into five groups: normal control (NC), high-fat/cholesterol control (HC), tannin in HFD (HT, 1% of diet), immature persimmon in HFD (HI, 7% of diet), and mature persimmon in HFD (HM, 7% of diet). Tannin was used as a positive control. Biochemical, molecular, and histopathological changes were observed in the blood and liver. Results: We confirmed that a high fat/cholesterol diet successfully induced dyslipidemia, which was characterized by significantly altered lipid profiles in the plasma and liver. However, oxidized low-density lipoprotein levels, histopathological damage in the liver, and hepatic Triglyceride levels were significantly reduced in all HT, HI, and HM groups compared to those in the HF group. In contrast, plasma apolipoprotein B level was significantly reduced only in the HT and HM groups, whereas reduction of the LDL-C level was detected only in the HI group. Although HF-induced sterol regulatory element-binding protein (SREBP) gene expression was significantly reduced in all treated groups, downstream gene expression levels varied among the different groups; significant reduction of fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-CoA (HMGCR) gene expression was detected only in the HI group, whereas cholesterol 7α-hydroxylase (CYP7A1) gene expression was significantly elevated only in the HM group. Conclusion: Taken together, the data suggest that protection of LDL oxidation and hepatic lipogenesis might be, at least partly, attributed to tannin in persimmons. However, the identified mechanisms varied up to the maturation stage of persimmon. In the case of immature persimmon, modulation of FAS and HMGCR gene expression was prominent, whereas in the case of mature persimmon, modulation of CYP7A1 gene expression was prominent.
In this study, immature persimmon (Diospyros kaki Thunb.) ethanol extract was administered to an obese animal model fed a high-fat diet to measure weight change, adipose tissue weight, serum lipid level, and expression level of adipose-related genes to evaluate its efficacy. Administration of D. kaki ethanol extract (DKE) (100 and 500 mg/kg/d) decreased the body weight gain, adipose tissue weight, and serum Triglyceride levels in mice fed a high-fat diet. Furthermore, it improved the leptin and adiponectin levels in the blood as well as gene expression in the liver. It also inhibited the expression of sterol regulatory element-binding protein-1c, inhibiting the production of Triglyceride biosynthetic enzyme fatty acid synthesis and acetyl-CoA carboxylase, and decreased the expressions of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding proteins that induce adipocyte differentiation. Therefore, these data suggest that DKE exerts beneficial effects on high-fat diet-induced obesity by modulating lipid metabolism in mice fed a high-fat diet.
This study aimed to investigate the potential of freeze-dried persimmon powder (Diospyros kaki Thumb.) to protect against dyslipidemia induced by a high-fat/cholesterol diet (HFD) in a rat model. Methods: Fifty Wistar rats were randomly divided into five groups: normal control (NC), high-fat/cholesterol control (HC), tannin in HFD (HT, 1% of diet), immature persimmon in HFD (HI, 7% of diet), and mature persimmon in HFD (HM, 7% of diet). Tannin was used as a positive control. Biochemical, molecular, and histopathological changes were observed in the blood and liver. Results: We confirmed that a high fat/cholesterol diet successfully induced dyslipidemia, which was characterized by significantly altered lipid profiles in the plasma and liver. However, oxidized low-density lipoprotein levels, histopathological damage in the liver, and hepatic Triglyceride levels were significantly reduced in all HT, HI, and HM groups compared to those in the HF group. In contrast, plasma apolipoprotein B level was significantly reduced only in the HT and HM groups, whereas reduction of the LDL-C level was detected only in the HI group. Although HF-induced sterol regulatory element-binding protein (SREBP) gene expression was significantly reduced in all treated groups, downstream gene expression levels varied among the different groups; significant reduction of fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-CoA (HMGCR) gene expression was detected only in the HI group, whereas cholesterol 7α-hydroxylase (CYP7A1) gene expression was significantly elevated only in the HM group. Conclusion: Taken together, the data suggest that protection of LDL oxidation and hepatic lipogenesis might be, at least partly, attributed to tannin in persimmons. However, the identified mechanisms varied up to the maturation stage of persimmon. In the case of immature persimmon, modulation of FAS and HMGCR gene expression was prominent, whereas in the case of mature persimmon, modulation of CYP7A1 gene expression was prominent.
Persimmon (Diospyros kaki) fruit: hidden phytochemicals and health claims
These beneficial effects may be due to the properties of its phenolic compounds (1.15 g / 100 g) and high fiber (63.48 g / 100 g) content (Innami et al., 1998[53]; Gorinstein et al., 1999[38]). In another study, Lee et al. (2006[77]) supplementation powdered whole persimmon leaf (5 %) and observed that supplementation results in lowering of blood cholesterol and Triglyceride, while increased ratio of HDL-C/total-C was also observed. In another study, Matsumoto et al. (2006[86]) supplemented diet with young persimmon fruit (10 %) that reslted in similar results i.e. lowering of total & LDL cholesterol and Triglyceride.
Docosahexaenoic Acid
Epidemiological and genetic studies suggest that elevated Triglyceride (TG)-rich lipoprotein levels in the circulation increase the risk of cardiovascular disease. Prescription formulations of omega-3 fatty acids (OM3FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma TG levels and are approved for the treatment of patients with severe hyperTriglyceridemia. Many preclinical studies have investigated the TG-lowering mechanisms of action of OM3FAs, but less is known from clinical studies.
EGb 761
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
A 12-week intervention with KRG was conducted in patients with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed with T2DM. Subjects were randomized in a double-blind, placebo-controlled trial. The trial results showed that 12 weeks of intervention with KRG supplementation (5 g/day) led to normalization of whole blood and serum glucose levels as well as serum insulin and CRP concentrations (Bang et al., 2014). Administration of Panax Ginseng extract (PGE) for 8 weeks (6 g/day) decreased serum Triglycerides and total cholesterol and LDL levels, while increasing HDL levels. These results were attributed to PGE potent antioxidant effects (Kim and Park, 2003). In accordance, the effects of a low-dose (3 g/day) and a high-dose (6 g/day) of KRG supplementation for 8 weeks on antioxidant enzymes and oxidative stress markers in humans were assessed in a randomized, double-blind, placebo-controlled trial. Increased GSH-Px, SOD, and CAT activities were found in the high-dose group as compared to the placebo group. Plasma oxidized-LDL levels and DNA tail length and tail moment were significantly decreased in both high and low dose groups but increased in the placebo group. This led to the conclusion that supplementation with KRG upregulates antioxidant enzymes activities and consequently attenuates lymphocyte DNA damage
Elaeocarpus Ganitrus
ANTIOXIDANT AND lipid lowering effectS OF ELAEOCARPUS GANITRUS INcholesterol FED RABBITS
Elaeocarpus ganitrus Roxb. is reported to exhibit multifarious pharmacological activities. However no scientific study has been conducted to evaluateAntiatherosclerotic /lipidlowering activity of E. ganitrus Roxb. The present study was designed to investigate the antihyperlipidaemic and antioxidant activity of 70% ethanolic extract of E. ganitrus seed (EGEE) incholesterol fed hyperlipidaemic rabbits. The EGEE was administered at a dose level of 250 and 500 mg/kg/day (p.o.) for 60 days to hyperlipidaemic rabbits.lipid profile inserum and antioxidant parameters in tissues (Liver, Heart and Aorta) were determined. The statistical analysis was carried out using one way ANOVA followed by Tukey’s multiple comparison tests. EGEE showed a decrease in the levels ofserum totalcholesterol, Triglycerides , phospholipids,LDL, VLDL (P ≤ 0.01, ≤ 0.001) in a dose dependant manner in treated animals. HDL ratioimproved profoundly as well as marked decline was noticed in atherogenic index after administration with EGEE. A considerable decrease inlipid per oxidation and a significant elevation in Glutathione, Catalase and SOD levels (P ≤ 0.01, ≤ 0.001) were observed in EGEE treated rabbits. The overall experimental results suggests that the biologically active phytoconstituents such as phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins present in the EGEE may be responsible for the significant hypolipidaemic as well as antioxidant activity, signifying the potential protective role in coronary heart disease.
ANTIOXIDANT AND LIPID LOWERING EFFECTS OF ELAEOCARPUS GANITRUS IN CHOLESTEROL FED RABBITS
Elaeocarpus ganitrus Roxb. is reported to exhibit multifarious pharmacological activities. However no scientific study has been conducted to evaluate antiatherosclerotic /lipid lowering activity of E. ganitrus Roxb. The present study was designed to investigate the antihyperlipidaemic and antioxidant activity of 70% ethanolic extract of E. ganitrus seed (EGEE) in cholesterol fed hyperlipidaemic rabbits. The EGEE was administered at a dose level of 250 and 500 mg/kg/day (p.o.) for 60 days to hyperlipidaemic rabbits. Lipid profile in serum and antioxidant parameters in tissues (Liver, Heart and Aorta) were determined. The statistical analysis was carried out using one way ANOVA followed by Tukey’s multiple comparison tests. EGEE showed a decrease in the levels of serum total cholesterol, Triglycerides, phospholipids, LDL, VLDL (P ≤ 0.01, ≤ 0.001) in a dose dependant manner in treated animals. HDL ratio improved profoundly as well as marked decline was noticed in atherogenic index after administration with EGEE. A considerable decrease in lipid per oxidation and a significant elevation in Glutathione, Catalase and SOD levels (P ≤ 0.01, ≤ 0.001) were observed in EGEE treated rabbits. The overall experimental results suggests that the biologically active phytoconstituents such as phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins present in the EGEE may be responsible for the significant hypolipidaemic as well as antioxidant activity, signifying the potential protective role in coronary heart disease.
The present study was designed to investigate the antiatherosclerotic and antioxidant activity of 70% ethanolic crude extract of Elaeocarpus ganitrus seed in cholesterol fed rabbits. The E. ganitrus extract was administered at a dose level of 250 and 500 mg/kg/day (p.o) for 120 days to cholesterol fed rabbits. Lipid profile in serum and tissue biochemistry as well as antioxidant parameters in heart were determined. The histological change in coronary artery was examined. Statistical analysis was carried out by using One way ANOVA followed by Tukey’s multiple comparison tests using Graphpad PRISM software (version 5). Rabbits fed with cholesterol and E. ganitrus extract concurrently showed significant (P ≤ 0.01, ≤ 0.001) decrease in the levels of serum total cholesterol, Triglycerides, phospholipids, LDL, VLDL and atherogenic index along with a considerable improvement in HDL ratio in a dose dependant manner. Further, a significant reduction was also recorded in the levels of total cholesterol, Triglycerides; phospholipids in heart of plant extract administered group animals. Lipid peroxidation levels decreases significanlty as well as marked elevation in Glutathione, Catalase and SOD levels were observed in treated group rabbits. Histopathological analysis revealed significant increase in lumen size of coronary arteries when E. ganitrus extract supplemented concurrently to cholesterol fed animals. Our study exhibited that the phytoconstituents like phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins present in the E. ganitrus ethanolic extract may be attributed to the significant antiatherosclerotic as well as antioxidant activity, signifying the potential protective role in coronary artery disease.
Emodin
Naturally OccurringPCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Rheum palmatum Linn has been widely applied in the clinical treatment of diabetes mellitus. It has been found that emodin as the major bioactive component of R. palmatum L exhibits the competency to activate peroxisomal proliferator-activated receptor-gamma (PPARgamma) in vitro. So the aim of this study was to evaluate the anti-diabetic effects of emodin through the activation of PPARgamma on high-fat diet-fed and low dose of streptozotocin (STZ)-induced diabetic mice. The diabetic mice were intraperitoneally injected with emodin for three weeks. No changes of food consumption and the body weight in emodin-treated mice were monitored daily during the entire experiment. At the end of experiment, the levels of blood glucose, Triglyceride and total cholesterol in serum were significantly decreased after emodin treatment. However, serum high-density lipoprotein cholesterol (HDLc) concentration was significantly elevated. The glucose tolerance and insulin sensitivity in emodin-treated group were significantly improved. Furthermore, the results of quantitative RT-PCR analysis showed that emodin significantly elevated the mRNA expression level of PPARgamma and regulated the mRNA expressions of LPL, FAT/CD36, resistin and FABPs (ap2) in liver and adipocyte tissues. No effects on the mRNA expressions of PPARalpha and PPARalpha-target genes were observed. Taken together, the results suggested that the activation of PPARgamma and the modulation of metabolism-related genes were likely involved in the anti-diabetic effects of emodin.
Emodin is an active herbal component traditionally used in China for treating a variety of diseases. The aim of this study was to examine the effect of emodin on the reducing lipid accumulation in white adipose tissue of high-fat diet-fed rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed a high-fat diet for two weeks, rats were dosed orally with emodin (20, 40, 80 mg/kg/day) or pioglitazone (20 mg/kg/day), once daily for eight weeks. Changes in body weight, feeding pattern, serum lipids, coronary artery risk index, and atherogenic index were investigated. Subcutaneous white adipose tissues were isolated for pathology histology and Western blot analyses. Changes of Triglyceride accumulation in differentiated 3 T3-L1 adipocytes were also investigated. Emodin exhibited a significant concentration-dependent decrease in the intracellular accumulation of Triglyceride in 3 T3-L1 adipocytes. Emodin (80 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing body weight gain and plasma lipid levels as well as the coronary artery risk and atherogenic indices of high-fat diet-fed rats. Emodin also caused dose related reductions in epididymal white adipose tissue sizes in high-fat diet-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase and its primary downstream targeting enzyme, acetyl-CoA carboxylase, upregulated gene expression of carnitine palmitoyl transferase 1, and downregulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the epididymal white adipose tissue of high-fat diet-fed rats. Our findings suggest that emodin could attenuate lipid accumulation in white adipose tissue through AMP-activated protein kinase activation.
The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of emodin on high-fat diet (HFD)-induced obese rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed HFD for two weeks, Wistar rats were dosed orally with emodin (40 and 80 mg kg−1) or pioglitazone (20 mg kg−1), once daily for eight weeks. Emodin (80 mg kg−1 per day) displayed similar characteristics to pioglitazone (20 mg kg−1 per day) in reducing body weight gain, plasma lipid levels as well as coronary artery risk index and atherogenic index of HFD-fed rats. Emodin also caused dose related reductions in the hepatic Triglyceride and cholesterol contents and lowered hepatic lipid droplets accumulation in HFD-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in hepatocytes of HFD-fed rats. Our findings suggest emodin could attenuate lipid accumulation by decreasing lipogenesis and increasing mitochondrial fatty acid β-oxidation mediated by activation of the AMPK signaling pathway.
Emodin Ameliorates Ethanol-Induced Fatty Liver Injury in Mice
The liver plays a central role in ethanol (EtOH) metabolism, and oxidative stress is implicated in alcohol-mediated liver injury. The present study aimed to investigate the role of emodin in EtOH-induced fatty liver injury. Liver histology, biochemistry and gene-expression studies were performed. Mice fed with an EtOH-containing diet exhibited severe macrovesicular steatosis and higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. However, emodin ameliorated liver steatosis and lowered ALT and AST. Emodin also decreased hepatic Triglyceride in mice fed with EtOH. In addition, emodin attenuates Oil Red O staining in alcoholic fatty liver in mice. Hepatic cytochrome P450 2E1 protein levels were upregulated in EtOH-fed mice, but downregulated in emodin-treated mice. In addition, emodin decreased hepatic oxidative stress. Furthermore, emodin significantly reduced liver α-smooth muscle actin and collagen type I, whereas it increased the mRNA levels of PPAR-γ. Taken together, emodin plays protective roles in alcohol-mediated liver steatosis.
EPA (Eicosapentaenoic Acid)
Eicosapentaenoic Acid (Epa) – Uses, Side Effects, and More
EPA prevents the blood from clotting easily, reduces Triglyceride levels in the blood, and has effects that might reduce pain and swelling.
EPA is a US FDA-approved prescription drug for reducing Triglyceride levels. As a supplement, people most commonly use EPA for heart disease, preventing heart attack, and depression. It is also used for chemotherapy-related side effects, diabetes, recovery after surgery, and many other purposes, but there is no good scientific evidence to support many of these other uses.
Don’t confuse EPA with similar fatty acids, such as alpha-linolenic acid and DHA. See the separate listings for algal oil, alpha-linolenic acid, DHA, fish oil, and krill oil.
Epigallocatechin gallate (EGCG)
effect of EGCG onlipidabsorption and plasmalipid levels in rats
Catechins, compounds derived from green tea, have been shown to reduce plasmacholesterol levels and the rate ofcholesterolabsorption. We investigated the dose response and the mechanism of action of epigallocatechin gallate (EGCG) on these parameters in rats. Wistar rats were fed adiethigh incholesterol and fat containing either none, 0.25% (0.2 g/day/kg BW), 0.5% (0.4 g/day/kg/BW) or 1.0% (0.7 g/day/kg BW) of EGCG. After 4 weeks of treatment, totalcholesterol and low density lipoprotein plasma levels were significantly reduced in the group fed 1% EGCG when compared to the no treatment group. Plasma Triglycerides andhigh-density lipoprotein levels did not change significantly. Following a single oral application of a liquid test-meal, intestinalcholesterolabsorption in Wistar rats was 79.3% in the control group. In the group treated with 0.1 g/kg BW EGCG intestinalcholesterolabsorption decreased to 73.7% and in the group treated with 0.5 g/kg BW of EGCG intestinalcholesterolabsorption fell significantly to 62.7% (P = 0.005). Total fatabsorption was very efficient in the control group (99.5% of the applied dose) and decreased significantly but moderately in the group treated with thehighest doses of EGCG (0.75, 1 g/kg BW). In an in-vitro biliary micelle model, the addition of 55 microM to 1300 microM EGCG not only decreasedcholesterol solubility dose-dependently in these micelles but also altered the size of the mixed lecithin/taurocholate/cholesterol micelles as demonstrated by light scattering. This study provides evidence suggesting that thecholesterol-loweringeffect of green tea is mainly elicited by EGCG, one of the most abundant catechins contained in green tea. It is suggested that one of the underlying mechanisms by which EGCG affectslipidmetabolism is by interfering with the micellar solubilization ofcholesterol in the digestive tract, which then in turn decreasedcholesterolabsorption.
The (−)-gallocatechin gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins, as a result of sterilization. The present study aims to examine the effects of GCG-rich tea catechins on hyperlipidemic rats and the mechanisms associated with regulating cholesterol metabolism in the liver. By performing heat epimerization of (−)-epigallocatechin gallate (EGCG), we manufactured a mixture of catechins that had a GCG content of approximately 50% (w/w). In sucrose-rich diet-induced hyperlipidemic rats, the GCG-rich tea catechins exhibited strong activity in reducing plasma cholesterol and Triglyceride concentrations. Furthermore, the hepatic cholesterol and Triglyceride concentrations that had increased as a result of the sucrose-rich diet were reduced due to GCG-rich tea catechins consumption. In order to investigate the hyperlipidemic mechanism of GCG-rich tea catechins, we examined the hepatic expressions of LDL receptor and HMG-CoA reductase in hyperlipidemic rats. We further evaluated the action of purified GCG on LDL receptor activity, which is a key contributor to the regulation of cholesterol concentrations. We found that purified GCG increased LDL receptor protein level and activity to a greater extent than EGCG. In conclusion, our study indicates that GCG-rich tea catechins in tea beverages may be effective in preventing hyperlipidemia by lowering plasma and hepatic cholesterol concentrations.
Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma Triglyceride levels (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are Triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.
Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma Triglyceride levels (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are Triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.
Eritadenine (Lentinus edodes)
Cardiovascular diseases are among the main causes of death in our society and there is a strong correlation between enhancedbloodcholesterol levels and the development of such diseases. The popular edible fungus, shiitake mushroom (Lentinus edodes), has been shown to produce abloodcholesterollowering compound designated eritadenine, and thehypocholesterolemic action of this compound has been quite extensively examined in rats. Eritadenine is suggested to accelerate the removal ofbloodcholesterol either by stimulating tissue uptake or by inhibiting tissue release; there are no indications of this compound inhibiting the biosynthesis ofcholesterol. If shiitake mushrooms are to be used as a source for a potentialcholesterolreducing product, it is of great importance to determine the content of eritadenine in the mushrooms as accurately as possible. Hence, in paper I methanol extraction was used to recover as much as possible of thehypocholesterolemic agent from the fungal cells. In order to analyse the target compound, a reliable and reproducible HPLC method for separation, identification and quantification of eritadenine was developed. The amounts of eritadenine in fruit bodies of four commercially cultivated shiitake mushrooms were determined, and the mushrooms under investigation exhibited up to ten times higher levels of eritadenine (3.17-6.33 mg/g dry mushrooms) than previously reported. Not only the fruit bodies of shiitake, but also its mycelia contain eritadenine. Growing fruit bodies of shiitake is a fairly demanding and time consuming process. Hence, in search for a source of eritadenine, submerged (liquid) cultivation of shiitake mycelia could be an alternative.
The hypocholesterolemic action of eritadenine in the rat
The hypolipidemic properties of eritadenine, an adenine derivative isolated from the Japanese mushroom Lentinus edodes, were investigated in rats with an emphasis on the effect on plasma cholesterol.
Eritadenine lowered all the plasma lipid levels (cholesterol, Triglyceride and phospholipid) and it was more than 10 times as active as clofibrate when administered in the diet. Large oral doses of eritadenine produced a hypocholesterolemic effect 3 hours after administration. Plasma free cholesterol was more affected than esterified cholesterol. Parenteral routes of administration did not seem to be as effective as the oral route. Dietary hypercholesterolemia was also suppressed by eritadenine. The acute Triton-induced hyperlipidemia was slightly suppressed by eritadenine, but proportionally less than in the normal rat. Although adenosine showed no effect on the hypocholesterolemic action of eritadenine, a twenty-fold excess of adenine may have interfered with the action of eritadenine.
Synthesis and hypocholesterolemic activities of eritadenine derivatives
Hypercholesterolemia is now considered a major risk factor in the development of premature atherosclerosis. Several classes of hypolipidemic agents are now available for the control of hypercholesterolemia. These include the HMG-CoA reductase inhibitors [1] which inhibit cholesterol biosynthesis, the second generation fibric acid derivatives [2] which interfere with fatty acid synthesis and stimulates hepatic fatty acid oxidation, thus reducing the amount of fatty acid available to the liver for Triglyceride synthesis, and the bile acid sequestrants [3] which interrupt the enterohepatic circulation of bile acids. The other types of hypocholest