ANTI-ADIPOGENIC (Adipocyte Differentiation Inhibitor)

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ANTI

ADIPOGENIC

200:1 CONCENTRATION

Adipogenesis refers to the process of formation of adipose tissue. It is a multistep process starting with clonal expansion of mesenchymal cells and the Differentiation of these mesenchymal cells into Pre-Adipocytes and finally into mature Adipocytes.

Herbal Remedies against Adipogenesis

Many phytochemicals and herbal extracts show Inhibitory effects on Adipogenesis in cell models and mouse models. However, lack of clinical evidence and epidemiological data to support their roles in Inhibiting Adipogenesis hindered their development to become an Anti-Obesity therapeutic agent. Furthermore, many of these phytochemicals have low bioavailability. Chemical structural modification or targeted delivery system may help to increase their Anti-Adipogenesis or Anti-Obesity efficacies. Nevertheless, many of these phytochemicals are abundantly found in our daily food, or they are the herbs for cooking or seasoning. For example, resveratrol is rich in red wine and grapes; genistein is rich in soy; quercetin in apples and onions, and curcumin is a well-known component of the cook seasoning. Therefore, a healthy diet can definitely help us to increase the uptake of these phytochemicals in our daily life. Moreover, combination of phytochemicals or herbal extracts may act synergistically to Inhibit Adipogenesis.

Indeed, Obesity is not simply an excess accumulation of white Adipose Tissue but is usually associated with insulin resistance and an increased production of metabolic hormones coupled with chronic low-grade state of Inflammation . To effectively Reduce Obesity , a holistic strategy with the consumption of phytochemicals or herbal extracts can be designed not only to Reduce Adipose Tissue Mass, but also increase thermogenic energy expenditure, improve insulin sensitivity, Reduce plasma lipids which can help to Reduce the Obesity -associated dyslipidemia and other comorbid conditions.

Potential of natural products in the Inhibition of Adipogenesis through regulation of PPARγ expression and/or its transcriptional activity

Obesity is a global health problem characterized as an increase in the Mass of Adipose Tissue . Adipogenesis is one of the key pathways that increases the Mass of Adipose Tissue , by which preAdipocyte s mature into Adipocytes through cell Differentiation . Peroxisome proliferator-activated receptor γ (PPARγ ), the chief regulator of Adipogenesis , has been acutely investigated as a molecular target for natural products in the development of anti-Obesity treatments. In this review, the regulation of PPARγ expression by natural products through Inhibition of CCAAT/enhancer-binding protein β (C/EBPβ) and the farnesoid X receptor (FXR), increased expression of GATA-2 and GATA-3 and activation of the Wnt/β-catenin pathway were analyzed.

Furthermore, the regulation of PPARγ transcriptional activity associated with natural products through the antagonism of PPARγ and activation of Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) were discussed. Lastly, regulation of mitogen-activated protein kinase (MAPK) by natural products, which might regulate both PPARγ expression and PPARγ transcriptional activity, was summarized. Understanding the role natural products play, as well as the mechanisms behind their regulation of PPARγ activity is critical for future research into their therapeutic potential for fighting Obesity.

Effects of Flavonoids and Phenolic Acids on the Inhibition of Adipogenesis in 3T3-L1 Adipocytes

Obesity has become a global epidemic in both developed and developing countries, and it is a significant risk factor for various diseases such as Diabetes , cancer, heart disease, and hypertension. In the present study, the effect of naturally occurring Antioxidants (Flavonoids and Phenolic Acids ) on the Inhibition of Adipogenesis in 3T3-L1 Adipocytes was investigated. The results showed that o-coumaric acid and rutin had the highest Inhibition on intracellular triglyceride (61.3 and 83.0%, respectively) among 15 Phenolic Acids and 6 Flavonoids tested. However, the oil red o stained material (OROSM) showed that cell number in 3T3-L1 Adipocytes was not influenced by those compounds.

For glycerol-3-phosphate dehydrogenase (GPDH) activity, the data indicated that o-coumaric acid and rutin had the highest Inhibition on GPDH activity (54.2 and 66.8%, respectively) among the compounds tested. o-Coumaric acid and rutin also Inhibited the expression of PPARγ , C/EBPα and leptin and then up-regulated expression of adiponectin at the protein level. Some naturally occurring Antioxidants efficiently suppressed Adipogenesis in 3T3-L1 Adipocytes. These results suggest that o-coumaric acid and rutin targeted for Adipocyte functions could be effective in improving the symptoms of Metabolic Syndrome.

INGREDIENTS & science

açai (Euterpe oleracea Martius)

Anti-lipidaemic and anti-inflammatory effect of açai (Euterpe oleracea Martius) Polyphenols on 3T3-L1 Adipocytes

AntiAdipogenic effects of açai seed extract on high fat diet-fed mice and 3T3-L1 Adipocytes : A potential mechanism of action

Acer okamotoanum Nakai Leaf Extract Inhibits Adipogenesis Via Suppressing Expression of PPAR γ and C/EBP α in 3T3-L1 cells

In this study, we observed that LEAO decreased the accumulation of lipid droplets during Adipogenesis and down-regulated the expression of key Adipogenic transcription factors such as peroxisome proliferator-activated receptor γ (PPAR γ) and CCAAT/enhancer binding protein α (C/EBP α). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote Adipogenesis by inducing the expression of PPAR γ. LEAO also activated β-catenin signaling, which prevents the Adipogenic program by suppressing the expression of PPAR γ. Therefore, we found that treatment with LEAO is effective for attenuating Adipogenesis in 3T3-L1 cells . Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing Obesity.

Adenanthin (isodon adenantha) 

The Effects of AICAR on Adipocyte Differentiation of 3T3-L1 cells

Ajoene Sulfur (Allium sativum)

Allium hookeri root

Andrographolide (Andrographis paniculata)

Andrographolide Inhibits Adipogenesis of 3T3-L1 cells by suppressing C/EBPβ expression and activation

Andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent Anti-Obesity action by Inhibiting PKA-CREB-mediated C/EBPβ expression as well as C/EBPβ transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression.

Anthocyanins 

Regulation of Adipocyte Function by Anthocyanins ; Possibility of Preventing the Metabolic Syndrome

Obesity is defined as the accumulation of excess Adipose Tissue resulting from various metabolic disorders. Adipocyte dysfunction is strongly associated with the development of Obesity and insulin resistance. Metabolic Syndrome is characterized by a group of metabolic risk factors in one person. Abdominal Obesity and Adipocyte dysfunction play an important role in the development of this syndrome.

Anthocyanins are used as a food coloring, and they are widely distributed in human diets including berries, suggesting that large amounts of Anthocyanins are ingested from plant-based foods. This study shows that Anthocyanins have a significant potency of AntiObesity and ameliorate Adipocyte function in in vitro and in vivo systems and also that they have important implications for preventing Metabolic Syndrome.

Antofine Alkaloid

Antrodia cinnamomea

Aqueous extract of Antrodia cinnamomea Reduced high-fat diet-induced Obesity in mice and suppressed Adipogenesis in 3T3-L1 cells

Apigetrin (apigenin-7-O-glucoside)  

Arctigenin

Arctiin Inhibits Adipogenesis in 3T3-L1 cells and decreases Adiposity and body weight in mice fed a high-fat diet

Aristolochia Manshuriensis 

Aristolochia Manshuriensis Kom Inhibits Adipocyte Differentiation by Regulation of ERK1/2 and Akt Pathway

Oral administration of AMK (62.5 mg/kg/day) significantly decreased the fat tissue weight, total cholesterol (TC), and low density lipoprotein-cholesterol (LDL-C) concentration in the blood. The results of this study suggested that AMK Inhibited lipid accumulation by the down-regulation of the major transcription factors of the adipogensis pathway including PPAR-γ and C/EBP-α through regulation of Akt pathway and ERK 1/2 pathway in 3T3-L1 Adipocytes and HFD-induced Obesity mice, and AA may be main act in Inhibitory effects of AMK during Adipocyte Differentiation.

Herbal Remedies against Adipogenesis

Aristolochia manshuriensis Kom is a traditional medicinal herb used for treatment of arthritis, rheumatism, hepatitis. Its extract Inhibited Adipocyte Differentiation by regulating ERK1/2 and Akt pathway. Besides, expressions of FAS, LPL and aP2 were significantly Reduced by the extract treatment during Adipogenesis.

Aristotelia chilensis

Antioxidant Capacity and in Vitro Inhibition of Adipogenesis and Inflammation by Phenolic Extracts of Vaccinium floribundum and Aristotelia chilensis

Interest in berries from South America has increased due to their potential health benefits. The objective of this study was to characterize the Anthocyanins and proanthocyanidins of Vaccinium floribundum and Aristotelia chilensis, total phenolics, and antioxidant capacity and to evaluate, in vitro, the ability of their phenolic extracts to Reduce Adipogenesis and lipid accumulation in 3T3-L1 Adipocytes. The anti-inflammatory property of these extracts on RAW 264.7 macrophages was also investigated. Antioxidant capacity, measured as oxygen radical scavenging capacity and expressed as Trolox equivalents, was higher in the berries of A. chilensis. Phenolic extracts Inhibited lipid accumulation by 4.0−10.8% when Adipocytes were treated at maturity and by 5.9−37.9% when treated throughout Differentiation.

Furthermore, a proanthocyanidin-enriched fraction from V. floribundum significantly increased Pref-1 expression in preadipocytes. Phenolic extracts decreased the production of nitric oxide (3.7−25.5%) and prostaglandin E₂ (9.1−89.1%) and the expression of inducible nitric oxide synthase (9.8−61.8%) and cycloxygenase-2 (16.6−62.0%) in lipopolysaccharide-stimulated RAW 264.7 macrophages. V. floribundum and A. chilensisphytochemicals limit Adipogenesis and inflammatory pathways in vitro, warranting further in vivo studies.

Aster yomena   

Ethanol extracts of Aster yomena (Kitam.) Honda Inhibit Adipogenesis through the activation of the AMPK signaling pathway in 3T3-L1 preadipocytes

Astilbe chinensis 

Astragalin (3-O-glucoside kaempferol) 

Averrhoa carambola

Obesity is associated with an increased risk of many chronic diseases. Recently, a growing body of evidence has shown that phytochemicals may Inhibit Adipogenesis and Obesity. In this study, we report for the first time, the ability of Averrhoa carambola L. peel extract commonly known as star fruit (SFP) to effectively suppress Adipocyte Differentiation in 3T3-L1 preadipocytes and therefore, address it as a potential candidate to treat Obesity and its related diseases. (−)-Epicatechin was identified as a bioactive compound likely responsible for this suppression.

As the genetic expression studies revealed that the Adipogenic activity of SFP extract was due to the simultaneous downregulation of the C/EBPα and PPARγ as well as the upregulation of PPARα receptor genes, a detailed computational docking study was also elucidated to reveal the likely binding mode of (−)-epicatechin to the receptor of interest, accounting for the likely mechanism that results in the overall suppression of Adipocyte Differentiation.

Avicularin (Guava leaves)

Avicularin, a Plant Flavonoid, Suppresses Lipid Accumulation through Repression of C/EBPα -Activated GLUT4-Mediated Glucose Uptake in 3T3-L1 cells

Avicularin (quercetin-3-O-α-l-arabinofuranoside) is a plant flavonoid and a quercetin glycoside. In this study, we found that avicularin suppressed the accumulation of intracellular lipids through repression of glucose transporter 4 (GLUT4)-mediated glucose uptake in mouse adipocytic 3T3-L1 cells. Avicularin was highly purified (purity of more than at least 99%) from Taxillus kaempferi (DC.) Danser (Loranthaceae) by high-performance liquid chromatography, and its structure was determined by nuclear magnetic resonance and Mass spectrometry. Avicularin decreased the intracellular triglyceride level along with a reduction in the expression of Adipogenic genes such as peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and aP2 (fatty acid-binding protein 4).

In contrast, avicularin did not affect the expression of lipogenic and lipolytic genes. Interestingly, the expression of the GLUT4 gene was significantly suppressed in an avicularin-concentration-dependent manner. Moreover, the binding of C/EBPα to the promoter region of the GLUT4 gene was repressed by adding avicularin to the medium in 3T3-L1 cells, as demonstrated by the results of a chromatin immunoprecipitation assay. These results indicate that avicularin Inhibited the accumulation of the intracellular lipids by decreasing C/EBPα-activated GLUT4-mediated glucose uptake in Adipocytes.

Bacaba (Oenocarpus bacaba)  

Bacaba phenolic extract attenuates Adipogenesis by down-regulating PPARγ and C/EBPα in 3T3-L1 cells

Bacaba (Oenocarpus bacaba Mart.) is a native Brazilian palm fruit with a high amount of Polyphenol ics, reported to have an apoptotic effect on cancer cells [1]. Here, we examined the effect of Bacaba phenolic extract (BPE) on Adipogenesis using 3T3-L1 preadipocytes . Proliferating and differentiating Adipocytes were incubated with BPE at 6, 12, and 24 μg of gallic acid equivalents (GAE)/ml. BPE Reduced accumulation of intracellular lipids and protein expression of Adipogenic markers including PPARγ, C/EBPα, FABP4, IR-β, and adiponectin in a dose-dependent manner during Differentiation of 3T3-L1 cells into Adipocytes.

Furthermore, lipid accumulation decreased with BPE (24 μg of GAE/ml) during the early stage of mitotic clonal expansion (Days 0–2). In contrast, the Inhibition of protein expression of Adipogenic markers needed a longer duration (Days 0–4, 0–7, 2–7) of BPE incubation. These results suggest that BPE Inhibits adipogenisis in vitro via targeting transcriptional factors during the early and middle stages of Differentiation.

Baicalin (Scutellaria baicalensis)

Bamboo (Phyllostachys bambusoides)

Banaba (Lagerstroemia speciosa)

An Extract of Lagerstroemia speciosa L. Has Insulin-Like Glucose Uptake–Stimulatory and Adipocyte Differentiation–Inhibitory Activities in 3T3-L1 Cells

The effects of extracts isolated from Lagerstroemia speciosa L. (banaba) on glucose transport and adipocyte differentiation in 3T3-L1 cells were studied. Glucose uptake–inducing activity of banaba extract (BE) was investigated in differentiated adipocytes using a radioactive assay, and the ability of BE to induce differentiation in preadipocytes was examined by Northern and Western blot analyses. The hot water BE and the banaba methanol eluent (BME) stimulated glucose uptake in 3T3-L1 adipocytes with an induction time and a dose-dependent response similar to those of insulin. Furthermore, there were no additive or synergistic effects found between BE and insulin on glucose uptake, and the glucose uptake activity of insulin could be reduced to basal levels by adding increasing amounts of BE.

Unlike insulin, BE did not induce adipocyte differentiation in the presence of 3-isobutyl-1-methylxanthine (IBMX) and dexamethasone (DEX). BE inhibited the adipocyte differentiation induced by insulin plus IBMX and DEX (IS-IBMX-DEX) of 3T3-L1 preadipocytes in a dose-dependent manner. The differences in the glucose uptake and differentiation inhibitory activities between untreated cells and those treated with BE were significant (P < 0.01). The inhibitory activity was further demonstrated by drastic reductions of peroxisome proliferator-activated receptor γ2 (PPARγ2) mRNA and glucose transporter-4 (GLUT4) protein in cells induced from preadipocytes with IS-IBMX-DEX in the presence of BE. The unique combination of a glucose uptake stimulatory activity, the absence of adipocyte differentiation activity and effective inhibition of adipocyte differentiation induced by IS-IBMX-DEX in 3T3-L1 cells suggest that BE may be useful for prevention and treatment of hyperglycemia and obesity in type II diabetics.

Benincasa hispida

Berberine

Berberine Inhibits Adipocyte Differentiation , proliferation and Adiposity through down-regulating galectin-3

Bergamottin (Bergamot)

Bergamottin Inhibits Adipogenesis in 3T3-L1 cells and Weight Regulation in Diet-Induced Obese Mice

Blumea balsamifera

Anti-Obesity Effect of Blumea balsamifera Extract in 3T3-L1 preadipocytes and Adipocytes

Obesity, the leading metabolic disease in the world, is a serious health problem in industrialized countries. We investigated the Anti-Obesity effect of Blumea balsamifera extract on Adipocyte Differentiation of 3T3-L1 preadipocytes and Anti-Obesity effect of 3T3-L1 Adipocytes. We found that treatment with an extract of Blumea balsamifera suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability in 3T3-L1 preadipocytes and Adipocytes.

Furthermore, Blumea balsamifera extract brought significant attenuation of expressions of key Adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)γ, CCAAT element binding protein (C/EBPs) and leptin, however, induced up-regulation of adiponectin at the protein level in 3T3-L1 preadipocytes and Adipocytes. These results suggest that Blumea balsamifera extract may block Adipogenesis, at least in part, by decreasing key Adipogenic transcription factors in 3T3-L1 preadipocytes and may have antiatherogenic, anti-inflammatory, and AntiDiabetic effects through up-regulation of adiponectin in 3T3-L1 Adipocytes.

Boldine (Peumus boldus)

The Aporphine Alkaloid Boldine Induces Adiponectin Expression and Regulation in 3T3-L1 cells

Adiponectin is an adipokine secreted by differentiated Adipocytes . Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with Metabolic Syndrome or cardiovascular disease. Natural compounds that can Prevent oxidative stress mediated Inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor (PPAR)-γ, in 3T3-L1 cells.

Differentiated 3T3-L1 Adipocytes were exposed to either hydrogen peroxide (H₂O₂) (100 μM) or tumor necrosis factor-α (TNFα) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5–100 μM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARγ, and C/EBPα to half of the control levels. Boldine, at all concentrations, counteracted the Inhibitory effect of H₂O₂ or TNFα and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5–25 μM) having a larger inductive effect compared to higher concentrations (50–100 μM). Boldine treatment alone in the absence of H₂O₂ or TNFα was also able to induce adiponectin at the inductive phase of Adipogenesis.

Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in Obesity-related cardiovascular disease.

Bromophenol (Polysiphonia morrowii)

Butein Chalconoid

Butein is a novel Anti-Adipogenic compound

Rhus verniciflua Stokes (RVS) has been used as a traditional herbal medicine for its various biological activities including Anti-Adipogenic effects. Activity-guided separation led to the identification of the Anti-Adipogenic functions of butein. Butein, a novel Anti-Adipogenic compound, robustly suppressed lipid accumulation and Inhibited expression of Adipogenic markers. Molecular studies showed that activated transforming growth factor-β (TGF-β) and suppressed signal transducer and activator of transcription 3 (STAT3) signaling pathways were mediated by butein. Analysis of the temporal expression profiles suggests that TGF-β signaling precedes the STAT3 in the butein-mediated Anti-Adipogenic cascade.

Small interfering RNA-mediated silencing of STAT3 or SMAD2/3 blunted the Inhibitory effects of butein on Adipogenesis indicating that an interaction between two signaling pathways is required for the action of butein. Upon butein treatments, stimulation of TGF-β signaling was still preserved in STAT3 silenced cells, whereas regulation of STAT3 signaling by butein was significantly impaired in SMAD2/3 silenced cells, further showing that TGF-β acts upstream of STAT3 in the butein-mediated anti-Adipogenesis.

Capsaicin

Effects of Capsaicin on Induction of Apoptosis and Inhibition of Adipogenesis in 3T3-L1 cells

Currently, at the beginning of the 21st century, Obesity has become the leading metabolic disease in the world. It is a serious health problem in industrialized countries. Previous research has suggested that decreased Preadipocyte Differentiation and proliferation and decreased lipogenesis are mechanisms to Reduce Obesity. In the present study, the effects of capsaicin on the induction of apoptosis and Inhibition of lipid accumulation in 3T3-L1 preadipocytes and Adipocytes were investigated. The results demonstrated that capsaicin decreased cell population growth of 3T3-L1 preadipocytes, assessed with the MTT assay. Flow cytometric analysis of 3T3-L1 preadipocytes exposed to capsaicin showed that apoptotic cells increased in a time- and dose-dependent manner. Treatment with capsaicin decreased the number of normal cells and increased the number of early apoptotic and late apoptotic cells in a dose-dependent manner.

The treatment of cells with capsaicin caused the loss of mitochondria membrane potential (ΔΨm). The induction of apoptosis in 3T3-L1 preadipocytes by capsaicin was mediated through the activation of caspase-3, Bax, and Bak, and then through the cleavage of PARP and the down-regulation of Bcl-2. Moreover, capsaicin significantly decreased the amount of intracellular triglycerides and glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 Adipocytes. Capsaicin also Inhibited the expression of PPARγ, C/EBPα, and leptin, but induced up-regulation of adiponectin at the protein level. These results demonstrate that capsaicin efficiently induces apoptosis and Inhibits Adipogenesis in 3T3-L1 preadipocytes and Adipocytes.

Carduus crispus

Inhibition of Adipocyte Differentiation by MeOH Extract from Carduus crispus through ERK and p38 MAPK Pathways

In this study, the effects of a methanol (MeOH) extract of Carduus crispus L. (Asteraceae) on Adipogenesis was investigated in 3T3-L1 cells. To differentiate preadipocytes to Adipocytes, confluent 3T3-L1 preadipocytes were treated with a hormone mixture, which included isobutylmethylxanthine, dexamethasone, and insulin (MDI). The methanol extract of C. crispus significantly decreased Fat Accumulation by Inhibiting Adipogenic signal transcriptional factors in MDI-induced 3T3-L1 cells in a dose-dependent manner.

In MTT assays and on PI-staining, methanol extract of C. crispus Inhibited the proliferation of 3T3-L1 cells during mitotic clonal expansion (MCE). The Anti-Adipogenic effect of the Carduus extract seemed to be associated with the up-regulation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways within the first 2 days after MDI treatment. These results suggest that methanol extract of C. crispus might be beneficial for the treatment of Obesity.

Carnosic acid (Salvia japonica Thunb.)

Carnosic acid and carnosol Inhibit Adipocyte Differentiation in mouse 3T3-L1 cells through induction of phase2 enzymes and activation of glutathione metabolism

In the previous studies, we reported that carnosic acid (CA) and carnosol (CS) originating from rosemary protected cortical neurons by activating the Keap1/Nrf2 pathway, which activation was initiated by S-alkylation of the critical cysteine thiol of the Keap1 protein by the “electrophilic”quinone-type of CA or CS. Here, we found that CA and CS Inhibited the in vitro Differentiation of mouse preadipocytes, 3T3-L1 cells, into Adipocytes. In contrast, other physiologically-active and rosemary-originated compounds were completely negative. These actions seemed to be mediated by activation of the antioxidant-response element(ARE) and induction of phase2 enzymes. This estimation is justified by our present findings that only CA and CS among rosemary-originated compounds significantly activated the ARE and induced the phase2 enzymes. Next, we performed cDNA microarray analysis in order to identify the gene(s) responsible for these biological actions and found that phase2 enzymes (Gsta2, Gclc, Abcc4, and Abcc1), all of which are involved in the metabolism of glutathione (GSH), constituted 4 of the top 5 CA-induced genes.

Celastrol (Tripterygium wilfordii)

Cascade regulation of PPARγ² and C/EBPα signaling pathways by celastrol impairs adipocyte differentiation and stimulates lipolysis in 3T3-L1 adipocytes

Materials/Methods: In order to address the questions above, we extended previous observations and investigated in vitro celastrol signaling study whether celastrol may regulate differentiation, lipolysis and key adipogenic transcriptional pathways in 3T3-L1 adipocytes.

Results: Treatment of celastrol not only inhibited adipocyte differentiation (lipid accumulation, glyceraldehyde-3-phosphate dehydrogenase activity and triglyceride content) but also increased lipolysis (glycerol release and free fatty acid release) in 3T3-L1 adipocytes. In addition, all celastrol-regulated functional activities were controlled by PPARγ² and C/EBPα signaling pathways in duration of celastrol’s treatment in 3T3-L1 adipocytes.

Chromolaena odorata  

Anti-Adipogenic effect of Flavonoids from Chromolaena odorata leaves in 3T3-L1 Adipocytes

Chrysanthemum zawadskii

Anti-Adipogenic Effects of Ethanol Extracts Prepared from Selected Medicinal Herbs in 3T3-L1 cells

Obesity is a major risk factor for various metabolic diseases such as cardiovascular disease, hypertension, and type 2 Diabetes mellitus. In this study, we prepared ethanol extracts from Agastache rugosa (ARE), Chrysanthemum zawadskii (CZE), Mentha arvensis (MAE), Perilla frutescens (PFE), Leonurus sibiricus (LSE), Gardenia jasminoides (GJE), and Lycopus coreanus (LCE). The anti-oxidant and Anti-Adipogenic effects were evaluated. The IC₅₀ values for ascorbic acid and LCE against 2,2-diphenyl-1-picrylhydrazyl radicals were 246.2 μg/mL and 166.2 μg/mL, respectively, followed by ARE (186.6 μg/mL), CZE (198.6 μg/mL), MAE (337.1 μg/mL), PFE (415.3 μg/mL), LSE (548.2 μg/mL), and GJE (626.3 μg/mL). In non-toxic concentration ranges, CZE had a strong Inhibitory effect against 3T3-L1 adipogenes (84.5%) than those of the other extracts.

Furthermore, the Anti-Adipogenic effect of CZE is largely limited in the early stage of Adipogenesis, and we revealed that the Inhibitory role of CZE in Adipogenesis is required for the activation of Wnt signaling. Our results provide scientific evidence that the Anti-Adipogenic effect of CZE can be applied as an ingredient for the development of functional foods and nutri-cosmetics for Obesity prevention.

 

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Chrysin (Oroxylum indicum)

Chrysin induces brown fat–like phenotype and enhances lipid metabolism in 3T3-L1 Adipocytes

Methods: Chrysin-induced fat browning was investigated by determining expression levels of brown fat–specific genes and proteins by real-time polymerase chain reaction and immunoblot analysis, respectively.

Results: Chrysin enhanced expression of brown fat–specific markers and increased protein levels of peroxisome proliferator-activated receptor (PPAR)α, PPARγ, PPARδ, phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase, hormone sensitive lipase, perilipin, carnitine palmitoyltransferase 1, acyl-coenzyme A oxidase 1, peroxisome proliferator-activated receptor-1 alpha (PGC-1α), and uncoupling protein 1 (UCP-1), suggesting its possible role in augmentation of Lipolysis, fat oxidation, and thermogenesis as well as reduction of lipogenesis. Increased expression of UCP-1 and other brown fat–specific markers was possibly mediated by chrysin-induced activation of AMPK based on the fact that Inhibition of AMPK by dorsomorphin abolished expression of PR domain-containing 16, UCP-1, and PGC-1α while the activator 5-aminoimidazole-4-carboxamide ribonucleotide elevated expression of these brown marker proteins.

Cinnamomum verum

Inhibition of Adipocyte Differentiation and Adipogenesis by supercritical fluid extracts and marc from Cinnamomum verum

Cirsium brevicaule 

Cirsium brevicaule A. GRAY leaf Inhibits Adipogenesis in 3T3-L1 cells and C57BL/6 mice

Results: Treatment of 3T3-L1 Adipocytes with a hexane extract of CL significantly Reduced cellular lipid accumulation and expression of the fatty acid synthase (FASN) gene. Dietary CL Reduced the serum levels of non-esterified fatty acids in HFD-fed mice. Significant decreases in subcutaneous WAT weight and associated FASN gene expression were observed in the mice fed the experimental CL diet. Dietary CL also Reduced the hepatic lipid and serum levels of a hepatopathic indicator in the HFD-fed mice. A significant reduction in mRNA levels of FASN and HMG-CoA reductase were observed in the livers of the CL-diet group. Dietary CL, on the other hand, increased in the hepatic mRNA levels of genes related to β-oxidation, namely peroxisome proliferator-activated receptor α, calnitine palmitoyltrasferase 1A, and uncoupling protein 2. Expression of the insulin receptor gene was also significantly increased in the livers of mice-fed the CL diet.

Conclusions: The present study therefore demonstrated that CL Suppresses lipid accumulation in the WAT and liver partly through Inhibiting mRNA levels of FASN gene and enhancing the Lipolysis -related gene expression.

Cirsium setidens 

Cirsium setidens Nakai, a wild perennial herb, grows mainly in Gangwon province, Korea, and has been reported to contain bioactive ingredients with various medicinal activities, including the treatment of edema, bleeding, and hemoptysis. However, the potential AntiObesity effects of C. setidens Nakai have not been fully investigated. This study evaluated the AntiObesity effect of standardized C. setidens Nakai ethanolic extract (CNE) in 3T3-L1 Adipocytes and in obese C57BL/6J mice fed a high-fat diet. CNE suppressed the expression of lipogenic genes and increased the expression of lipolytic genes. The AntiAdipogenic and antilipogenic effects of CNE appear to be mediated by the Inhibition of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBP) expressions.

Moreover, CNE stimulated fatty acid oxidation in an AMPK-dependent manner. CNE-treated groups of C57BL/6J mice showed Reduced body weights and Adipose Tissue weight and improved serum lipid profiles through the downregulation of PPARγ, C/EBPα, fatty acid binding protein 4 (FABP4), sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid synthase (FAS) and the upregulation of adiponectin and carnitine palmitoyltransferase-1 (CPT-1) in obese C57BL/6J mice fed a high-fat diet. These results suggest that CNE may have an AntiObesity effect on Adipogenesis and lipid metabolism in vitro and in vivo and present the possibility of developing a treatment for Obesity with nontoxic natural resources.

Citrus aurantium

Citrus aurantium Flavonoids Inhibit Adipogenesis through the Akt signaling pathway in 3T3-L1 cells

Clitoria ternatea

Clitoria ternatea Flower Petal Extract Inhibits Adipogenesis and Lipid Accumulation in 3T3-L1 preadipocytes by Downregulating Adipogenic Gene Expression

Clitoria ternatea (commonly known as blue pea) flower petal extract (CTE) is used as a natural colorant in a variety of foods and beverages. The objective of study was to determine the Inhibitory effect of CTE on Adipogenesis in 3T3-L1 preadipocytes. The phytochemical profiles of CTE were analyzed by liquid chromatography and tandem Mass spectrometry (LC-MS/MS). Anti-Adipogenesis effect of CTE was measured by using Oil Red O staining, intracellular triglyceride assay, quantitative real-time PCR and western blot analysis in 3T3-L1 Adipocytes. Cell cycle studies were performed by flow cytometry. Lipolysis experiments were performed using a colorimetric assay kit. In early stages, CTE demonstrated Anti-Adipogenic effects through Inhibition of proliferation and cell cycle retardation by suppressing expression of phospho-Akt and phospho-ERK1/2 signaling pathway.

The results also showed that CTE Inhibited the late stage of Differentiation through diminishing expression of Adipogenic transcription factors including PPARγ and C/EBPα. The Inhibitory action was subsequently attenuated in downregulation of fatty acid synthase and acetyl-CoA carboxylase, causing the reduction of TG accumulation. In addition, CTE also enhanced catecholamine-induced Lipolysis in Adipocytes. These results suggest that CTE effectively attenuates Adipogenesis by controlling cell cycle progression and downregulating Adipogenic gene expression.

Camellia ptilophylla

Cocoa tea (Camellia ptilophylla) water extract Inhibits Adipocyte Differentiation in mouse 3T3-L1 preadipocytes

Cocoa tea (Camellia ptilophylla) is a naturally decaffeinated tea plant. Previously we found that cocoa tea demonstrated a beneficial effect against high-fat diet induced Obesity , hepatic steatosis and hyperlipidemia in mice. The present study aimed to investigate the Anti-Adipogenic effect of cocoa tea in vitro using preadipocytes 3T3-L1. Adipogenic Differentiation was confirmed by Oil Red O stain, qPCR and Western blot. Our results demonstrated that cocoa tea significantly Inhibited triglyceride accumulation in mature Adipocytes in a dose-dependent manner. Cocoa tea was shown to suppress the expressions of key Adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPAR γ) and CCAAT/enhancer binding protein (C/EBP α).

Colocynth (Citrullus colocynthis)

Colocynth (Citrullus colocynthis) seed extracts attenuate Adipogenesis by down-regulating PPARγ / SREBP-1c and C/EBPα in 3T3-L1 cells

Adipogenesis is the overall process of Adipocyte Differentiation. With a positive energy balance, intracellular accumulation of triglyceride increases through the generation of functional Adipocytes. This occurs with Adipogenesis of undifferentiated preadipocytes. Citrullus colocynthis (CC), a member of the Cucurbitaceae family, is a desert viny plant native to North Africa. The effect of ethanolic seed extracts of colocynth (SCEE) on Adipogenesis was investigated using 3T3-L1 preadipocytes. Cell viability was measured using the MTT assay; triglycerides were stained with Oil Red O and Adipogenesis-related gene expressions were quantified using qRT-PCR. Results showed that SCEE helps to Inhibit intracellular triglyceride accumulation during Adipogenesis without affecting cell viability. Likewise, SCEE not only showed Anti-Adipogenic activities, essentially during the early stage, but their effects during the middle and late stages were very low.

Coptis chinensis

Effect of Atractylodes Rhizoma Alba, Houttuyniae Herba, Lonicerae Flos, Scutellariae Radix and Coptidis Rhizoma Extracts Combined with Metformin on the Antioxidant and Adipocyte Differentiate Inhibition

Objectives: This study was to investigate the antioxiative capacity, AntiObesity effects of Atractylodes Rhizoma Alba, Houttuyniae Herba, Lonicerae Flos, Scutellariae Radix, and Coptidis Rhizoma on Raw 264.7 and 3T3-L1 cell lines.

Methods: Three different types of herb extracts (A. Rhizoma Alba, H. Herba, L. Flos, S. Radix, and C. Rhizoma; water 100%, ethanol 30%, ethanol 100%) were used in this study. Total Polyphenol compound, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, reactive oxygen species (ROS) activity, NO production and cell proliferation were measured.

Results: Total Polyphenol compound measurement of L. Flos, A. Rhizogenes, and C. Rhizoma extracts were higher than A. Rhizoma Alba, H. Herba. DPPH radical scavenging activity, ROS activity and NO production of S. Radix, C. Rhizoma extracts were lower than L. Flos, A. Rhizoma, and H. Herba.

Conclusions: Metformin and S. Radix, C. Rhizoma, A. Rhizoma Alba, and L. Flos extracts combination groups showed synergistic effect on Adipocyte Differentiation Inhibition and antioxidative activity.

Cordycepin (Cordyceps sinensis)

The Effects of Cordyceps sinensis (Berk.) Sacc. and Gymnema inodorum (Lour.) Decne. Extracts on Adipogenesis and Lipase Activity In Vitro

This study aimed to investigate the effects of Cordyceps sinensis extract (CSE) and Gymnema inodorum extract (GIE), used alone and combined, on AntiAdipogenesis in 3T3-L1 cells . Oil Red O staining was used to examine the effects of these extracts on Inhibition of intracellular lipid accumulation in 3T3-L1 Adipocytes and on lipid droplet morphology. Fourier transform-infrared (FTIR) microspectroscopy was used to examine biomolecular changes in 3T3-L1 Adipocytes . The pancreatic lipase assay was used to evaluate the Inhibitory effects of CSE and GIE on pancreatic lipase activity.

Taken together, the results indicated that CSE, GIE, and their combination suppressed lipid accumulation. The FTIR microspectroscopy results indicated that CSE, GIE, and their combination had Inhibitory effects on lipid accumulation in the Adipocytes. Compared with the untreated Adipocytes, the signal intensity and integrated areas of glycogen and other carbohydrates, the acyl chain of phospholipids, and the lipid/protein ratios of the CSE, GIE, alone, and combined treated Adipocytes were significantly lower (p < 0.05). Combination treatment resulted in a synergistic effect on lipid accumulation reduction in the Adipocytes. Principal component analysis of the biomolecular changes revealed six distinct clusters in the FTIR spectra of the sample cells. The pancreatic lipase assay results indicated that CSE and GIE Inhibited the pancreatic lipase activity in a dose-dependent manner (mean ± standard error of the mean IC₅₀ values, 2312.44 ± 176.55 μg mL⁻¹ and 982.24 ± 44.40 μg mL⁻¹, resp.). Our findings indicated that FTIR microspectroscopy has potential application for evaluation of the effectiveness of medicinal plants and for the development of infrared biochemical Obesity markers useful for treating patients with Obesity.

Coumestrol 

Coumestrol modulates Akt and Wnt/β-catenin signaling during the attenuation of Adipogenesis

Coumestrol is a natural phytochemical present in plants such as red clover and soy, and has been reported to stimulate the estrogen receptor as a major phytoestrogen. While the molecular mechanisms responsible for the Anti-Adipogenic effects of phytoestrogens such as genistein and daidzein have been previously investigated, the effects of coumestrol on Adipogenesis remain to be elucidated. We observed that coumestrol dose-dependently attenuates MDI (mixture of 3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-induced lipid accumulation, consistent with an earlier study, while significantly Inhibiting MDI-induced Adipogenesis in the first 48 hours of Differentiation, a critical time window for Anti-Adipogenic effects. Coumestrol treatment suppressed MDI-induced protein expression of PPARγ and C/EBPα in Adipocytes, leading to the subsequent downregulation of FAS and aP2 expression. Akt and GSK3β were phosphorylated shortly after MDI stimulation, and these responses were Inhibited by coumestrol treatment.

Coumestrol also increased LRP6 protein expression, resulting in the recovery of β-catenin downregulation by MDI, while attenuating MDI-induced downregulation of Wnt10b. In addition, mRNA and protein expression of c-Myc and cyclin D1, target genes of β-catenin, were both recovered by coumestrol treatment. These results suggest that coumestrol Inhibits Adipocyte Differentiation via regulation of Akt and Wnt/β-catenin signaling and may have potential for development as an agent to Prevent Adipogenesis.

Cranberry (Oxycoccus quadripetalus)

Cranberries (Oxycoccus quadripetalus) Inhibit Adipogenesis and lipogenesis in 3T3-L1 cells

Cryptotanshinone (Salvia miltiorrhiza)

Cryptotanshinone, a compound of Salvia miltiorrhiza Inhibits Pre-Adipocytes Differentiation by regulation of Adipogenesis -related genes expression via STAT3 signaling

Purpose: The present study was designed to determine the in vitro Anti-Adipogenic effect and underlying molecular mechanisms of CT using 3T3-L1 murine Pre-Adipocytes .

Methods: We measured the levels of intracellular triglyceride accumulation and mRNA and protein expression of key Adipogenic transcription factors and their target genes.

Results: Treatment with CT drastically Reduced lipid accumulation in a dose- and time-dependent manner. Molecular assays showed that CT effectively suppressed the expression of C/EBPβ, C/EBPα , and PPARγ and of their target Adipocyte -specific genes aP2, adiponectin, and GLUT4 but activated the expression of Anti-Adipogenic genes such as GATA2, CHOP10, and TNF-α. CT treatment also Inhibited the phosphorylation of STAT3 in the early phase of Adipogenesis . A small-interfering-RNA-mediated knock-down of STAT3 potentiated the Anti-Adipogenic effect of CT.

Curcumin

Modification of Curcumin with Polyethylene Glycol Enhances the Delivery of Curcumin in preadipocytes and Its AntiAdipogenic Property

Conjugation of curcumin (CCM) by polyethylene glycol (PEG) has been previously developed to improve water solubility of the natural form of CCM and its antiproliferative role in some human cancer cell lines. This study examined the cellular uptake kinetics of the natural form of CCM and CCM−PEG. Their cytotoxic effect in proliferating preadipocytes and AntiAdipogenic property in differentiating preadipocytes had also been investigated. CCM and CCM−PEG were found to be differently absorbed in 3T3-L1 preadipocytes and Adipocytes with a limited amount of CCM−PEG absorption in the cell. The improved water solubility of CCM−PEG was correlated with increased cellular retention of CCM in 3T3-L1 cells, particularly in preadipocytes.

Consequently, CCM−PEG treatment sensitized proliferating preadipocytes to CCM-induced cell toxicity. Furthermore, incubation of differentiating 3T3-L1 cells with CCM−PEG resulted in improvement of the Inhibitory role of CCM in Adipocyte Differentiation with no toxic effect. These results suggest that pegylation-improved water solubility and cellular retention of CCM may be uniquely useful for improving the delivery of CCM in preadipocytes and its AntiAdipogenic ability.

Cyanidine-3-O-Galactoside (Aronia melanocarpa)

Cyanidin-3-O-galactoside-enriched Aronia melanocarpa extract attenuates Weight Gain and Adipogenic pathways in high-fat diet-induced obese C57BL/6 mice

Cyclopia subternata

Cyclopia maculata and Cyclopia subternata (honeybush tea) Inhibits Adipogenesis in 3T3-L1 Pre-Adipocytes

The stems, leaves and flowers of Cyclopia have been consumed as aherbal tea ‘honeybush tea’ to treat various medical ailments since the 19th century. Plant Polyphenols are reported to Inhibit Adipogenesis in cell and animal models of Obesity. The aim of this study was to assess the effect of hot water extracts of two Cyclopia species, C. maculata and C. subternata on Obesity in an in vitro model. The total Polyphenol content of unfermented C. subternata, unfermented C. maculata and fermented C. maculata extracts was 25.6, 22.4 and 10.8 g GAE/100 g, respectively.

The major compounds present in the extracts were: the flavonoid, phloretin-3′,5′-di-C-glucoside in C. subternata, the xanthone, mangiferin in unfermented C. maculata and the flavanone, hesperidin in fermented C. maculata. All of the plant extracts Inhibited intracellular triglyceride and Fat Accumulation, and decreased PPARγ 2 expression. The higher concentrations of unfermented C. maculata (800 and 1600 μg/ml) and C. subternata(1600 μg/ml) were cytotoxic in terms of decreased mitochondrialdehydrogenase activity. Both fermented and unfermented C. maculata, at concentrations greater than 100 μg/ml, decreased cellular ATPcontent. Cyclopia maculata and C. subternata Inhibit Adipogenesis in vitro, suggesting their potential as Anti-Obesity agents.

Cyclopia maculata (honeybush tea) stimulates Lipolysis in 3T3-L1 Adipocytes

Delphinidin-3-O–β-glucoside (D3G) is a health-promoting anthocyanin whose Anti-Obesity activity has not yet been thoroughly investigated. We examined the effects of D3G on Adipogenesis and lipogenesis in 3T3-L1 Adipocytes and primary white Adipocytes using real-time RT-PCR and immunoblot analysis. D3G significantly Inhibited the accumulation of lipids in a dose-dependent manner without displaying cytotoxicity. In the 3T3-L1 Adipocytes, D3G downregulated the expression of key Adipogenic and lipogenic markers, which are known as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1), CCAAT/enhancer-binding protein alpha (C/EBPα ), and fatty acid synthase (FAS).

Moreover, the relative protein expression of silent mating type information regulation 2 homolog 1 (SIRT1) and carnitine palmitoyltransferase-1 (CPT-1) were increased, alongside Reduced lipid levels and the presence of several small lipid droplets. Furthermore, D3G increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which suggests that D3G may play a role in AMPK and ACC activation in Adipocytes. Our data indicate that D3G attenuates Adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling, and, hence, could have a therapeutic role in the management and treatment of Obesity.

Anti-Adipogenic effects of delphinidin–3–O–β–glucoside in 3T3-L1 preadipocytes and primary white Adipocytes

Abstract Delphinidin–3–O–β–glucoside (D3G) is a health-promoting anthocyanin whose anti–Obesity activity has not yet been thoroughly investigated. We examined the effects of D3G on Adipogenesis and lipogenesis in 3T3-L1 Adipocytes and primary white Adipocytes.

DHEA

Dehydroepiandrosterone (DHEA) treatment in vitro Inhibits Adipogenesis in human omental but not subcutaneous Adipose Tissue

Dehydroepiandrosterone (DHEA), a precursor sex steroid, circulates in sulphated form (DHEAS). Serum DHEAS concentrations are inversely correlated with Metabolic Syndrome components and in vivo/in vitro studies suggest a role in modulating adipose Mass. To investigate further, we assessed the in vitro biological effect of DHEA in white (3T3-L1 ) and brown (PAZ6) Preadipocyte cell lines and human primary preadipocytes.

Diallyl trisulphide (onion)

AntiObesity effects of quercetin-rich onion peel extract on the Differentiation of 3T3-L1 preadipocytes and the Adipogenesis in high fat-fed rats

The aim of the present study was to examine the effect of quercetin-rich onion peel extract (OPE) on anti-Differentiation in 3T3-L1 preadipocytes and the AntiObesity in high-fat fed rats. We found that lipid accumulations and TG contents in 3T3-L1 cells were markedly suppressed by OPE. The mRNA levels of activating protein (AP2) were down-regulated and those of carnitine palmitoyl transferase-1 α (CPT-1α) and fatty acid binding protein 4 (FABP4) were up-regulated by 75 and 100 μg/ml OPE. Body weight, retroperitoneal and mesenteric fat weights of SD rats were significantly lower in the 8 week high fat (HF) diet + 0.72% OPE group than in the HF group.

Peroxisome proliferator-activated receptor (PPAR)γ mRNA levels were down-regulated in the epididymal fat of OPE than those of control and HF, and significant down-regulation of CCAAT/enhancer binding protein (C/EBP)α mRNA levels in OPE was also observed than the control. The mRNA levels of CPT-1α and uncoupling protein-1 (UCP-1) were up-regulated by the OPE, while those of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were down-regulated in HF and OPE groups compared to control group. These results suggest that quercentin-enriched OPE may have AntiObesity effects by suppressing Preadipocyte Differentiation and Inhibiting Adipogenesis.

Dioscin (Dioscorea japonica)

Dioscin Inhibits Adipogenesis through the AMPK/MAPK pathway in 3T3-L1 cells and modulates Fat Accumulation in obese mice

Dioscin (DS) is a steroidal saponin present in a number of medicinal plants and has been shown to exert anticancer, antifungal and antiviral effects. The present study aimed to deternube the effects DS on the regulation of Adipogenesis and to elucidate the underlying mechanisms. In vitro experiments were performed using differentiating 3T3-L1 cells treated with various concentrations (0-4 µM) of DS for 6 days. A cell viability assay was performed on differentiating cells following exposure to DS. Oil Red O staining and triglyceride content assay were performed to evaluate the lipid accumulation in the cells. We also carried out the following experiments: i) flow cytometry for cell cycle analysis, ii) quantitative reverse transcription polymerase chain reaction for measuring Adipogenesis-related gene expression, and iii) western blot analysis to measure the expression of Adipogenesis transcription factors and AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and mitogen-activated protein kinase (MAPK) phosphorylation.

In vivo experiements were performed using mice with Obesity induced by a high-fat diet (HFD) that were treated with or without DS for 7 weeks. DS suppressed lipid accumulation in the 3T3-L1 cells without affecting viability at a dose of up to 4 µM. It also delayed cell cycle progression 48 h after the initiation of Adipogenesis. DS Inhibited Adipocyte Differentiation by the downregulation of Adipogenic transcription factors and attenuated the expression of Adipogenesis-associated genes. In addition, it enhanced the phosphorylation of AMPK and its target molecule, ACC, during the Differentiation of the cells. Moreover, the Inhibition of Adipogenesis by DS was mediated through the suppression of the phosphorylation of MAPKs, such as extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK).

DS significantly Reduced Weight Gain in the mice with HFD-induced Obesity; this was evident by the suppression of Fat Accumulation in the abdomen. the present study reveals an Anti-Adipogenic effect of DS in vitro and in vivo and highlights AMPK/MAPK signaling as targets for DS during Adipogenesis.

Chenopodium formosanum

The Inhibitory Effects of Djulis (Chenopodium formosanum) and Its Bioactive Compounds on Adipogenesis in 3T3-L1 Adipocytes

The aim of this study was to provide new insights into the role of the ethanolic extracts of Djulis (Chenopodium formosanum, EECF) and its bioactive compounds in preventing Adipogenesis in 3T3-L1 Adipocytes. The results demonstrated EECF significantly Inhibited oil red O-stained material (OROSM), triglyceride levels and glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 Adipocytes. The expression of the critical molecules involved in lipid synthesis such as PPARγ, C/EBPα and SREBP-1c was attenuated in EECF-treated cells. According to HPLC-DAD and HPLC-MS/MS analysis, rutin, kaempferol, betanin and another nine compounds were present in EECF. The suppression of lipid accumulation by rutin, kaempferol and betanin occurred by decreasing the gene expression of PPARγ, C/EBPα and SREBP-1c. Taken together, these findings suggest the presence of bioactive compounds in EECF may partly account for the anti-Adipogenesis of EECF and EECF is therefore a potentially lipid lowering functional food.

Dolichos lablab 

Anti–Obesity activities of chikusetsusaponin IVa and Dolichos lablab L. seeds

Obesity, a condition where excess body fat accumulates to the extent, causes a negative effect on health. Previously, we reported the extract of Dolichos lablab L. (DLL-Ex) Inhibited high-fat diet (HFD)-induced increases in body weight and body fat Mass and ameliorated increases in body weight. In the present work, we studyed the molecular mechanism for the Inhibitory effect of DLL-Ex or Chikusetsusaponin IVa (CS-IVa), as isolated from Dolichos lablab L. (DLL) seeds extract, on Adipocyte Differentiation . We evaluated the effect of DLL-Ex, an Anti-Obesity agent, and CS-IVa, an active component of DLL-Ex, on 3T3-L1 cell Differentiation via Oil red O assay and Q-PCR, along with their effects on CCAAT element binding protein alpha (C/EBPα ), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), and fatty acid-binding protein 4 (FABP4) mRNA transcriptions. FAS and FABP4 protein expression levels after exposure to CS-IVa were also tested. The results showed that DLL-Ex and CS-IVa have potent Inhibitory activity on Adipocyte Differentiation. Therefore, DLL and CS-IVa may be developed as a functional food material to treat Obesity.

Ecklonia Cava

Dieckol, a phlorotannin isolated from a brown seaweed, Ecklonia cava, Inhibits Adipogenesis through AMP-activated protein kinase (AMPK) activation in 3T3-L1

•The Ecklonia cava extract tested herein evidenced profound Adipogenesis Inhibition.

•The three Polyphenol compounds of phlorotannins were isolated from E. cava.

•Dieckol exhibited greatest potential Adipogenesis Inhibition.

Ecliptal (Eclipta alba)

Ecliptal, a promising natural lead isolated from Eclipta alba modulates Adipocyte function and Ameliorates Metabolic Syndrome

Ethyl acetate fraction of Eclipta alba: a potential phytopharmaceutical targeting Adipocyte Differentiation

Egcg

The Anti-Adipogenic effects of (-) epigallocatechin gallate are dependent on the WNT/β-catenin pathway

(-)Epigallocatechin gallate (EGCG) is the most abundant catechin in green tea and reportedly has anti-obesity and anti-adipogenic effects. In this study, we determined that the up-regulation of the WNT/β-catenin pathway is the anti-adipogenic mechanisms of EGCG in 3T3-L1 cells. EGCG treatment down-regulates the expression of major genes involved in the adipogenesis pathway including peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer binding protein (C/EBP)α, fatty acid binding protein (FABP)4 and fatty acid synthase (FASN), while up-regulating the nuclear level of β-catenin. Knockdown of β-catenin using small interfering (si) RNA attenuated the inhibitory effects of EGCG on intracellular lipid accumulation. β-catenin siRNA transfection also recovered terminal adipocyte markers such as FABP4, FASN, lipoprotein lipase and adiponectin, which were down-regulated by EGCG. The DNA binding activities as well as the expression levels of PPARγ and C/EBPα, which were down-regulated by EGCG, were significantly restored by β-catenin siRNA transfection. In addition, we found that EGCG efficiently up-regulates the WNT/β-catenin pathway. Among the members of the WNT/β-catenin pathway, the expressions of low density lipoprotein receptor-related protein (LRP)5, LRP6, disheveled (DVL)2 and DVL3 were significantly up-regulated, while AXIN expression was down-regulated by EGCG, and the phosphorylation of glycogen synthase kinase 3β was increased. These results suggest that EGCG activates the WNT/β-catenin pathway, resulting in the up-regulation of β-catenin, which down-regulates the major genes of the adipogenesis pathway. Taken together, our findings clearly show that the anti-adipogenic effects of EGCG are, at least partially, dependent on the WNT/β-catenin pathway.

Fatty acid synthase (FAS) has been recognized as a potential therapeutic target for Obesity. In this study, for the first time, the Inhibitory effect of pomegranate husk extract, punicalagin and ellagic acid on FAS was investigated. We found them potently Inhibiting the activity of FAS with half-Inhibitory concentration values (IC₅₀) of 4.1 μg/ml (pomegranate husk extract), 4.2 μg/ml (4.50 μM, punicalagin) and 1.31 μg/ml (4.34 μM, ellagic acid), respectively. Moreover, they all exhibited time-dependent inactivation of FAS.

Punicalagin and ellagic acid Inhibited FAS with different mechanisms compared to previously reported Inhibitors, through inactivating acetyl/malonyl transferase and β-ketoacyl synthase domains, respectively. Additionally, 100 μg/ml pomegranate husk extract, 5.24 μg/ml (5 μM) punicalagin and 4.5 μg/ml (15 μM) ellagic acid effectively Reduced lipid accumulation inside FAS over-expressed 3T3-L1 Adipocytes. Since FAS plays a key role in the biosynthesis pathway of fatty acid, these findings suggest that pomegranate husk extract, punicalagin and ellagic acid have potential in the prevention and treatment of Obesity.

It has been reported that alkaloids derived from Coptis chinensis exert Anti-Adipogenic activity on 3T3-L1 Adipocytes by downregulating peroxisome proliferation-activity receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein-α (C/EBP-α). However, the signaling-based mechanism of the Inhibitory role of epiberberine in the early stages of 3T3-L1 Adipocyte Differentiation is uncharacterized. Here, we show that epiberberine had Inhibitory effects on Adipocyte Differentiation and significantly decreased lipid accumulation by downregulating an Adipocyte -specific transcription factor, sterol regulatory element-binding protein-1 (SREBP-1).

Furthermore, we observed that epiberberine markedly suppressed the Differentiation -mediated phosphorylation of components of both the Raf/mitogen-activated protein kinase 1 (MEK1)/extracellular signal-regulated protein kinase 1/2 (ERK1/2) and AMP-activated protein kinase-α1 (AMPKα)/Akt pathways. In addition, gene expression of fatty acid synthase (FAS) was significantly Inhibited by treatment with epiberberine during Adipogenesis . These results indicate that the Anti-Adipogenic mechanism of epiberberine is associated with Inhibition of phosphorylation of Raf/MEK1/ERK1/2 and AMPKα/Akt, followed by downregulation of the major transcription factors of Adipogenesis , such as PPAR-γ, C/EBP-α, and SREBP-1, and FAS. Taken together, this study suggests that the Anti-Adipogenic effect of epiberberine is mediated by downregulation of the Raf/MEK1/ERK1/2 and AMPKα/Akt pathways during 3T3-L1 Adipocyte Differentiation . Moreover, the Anti-Adipogenic effects of epiberberine were not accompanied by modulation of β-catenin.

Obesity is one of the major public health problems in the world because it is implicated in Metabolic Syndrome s, such as type 2 Diabetes , hypertension, and cardiovascular diseases. The objective of this study was to investigate whether Erigeron annuus (L.) Pers. (EAP) extract Suppresses reactive oxygen species (ROS) production and Fat Accumulation in 3T3-L1 cells by activating an AMP-dependent kinase (AMPK) signaling pathway. Our results showed that EAP water extract significantly Inhibits ROS production, Adipogenesis , and lipogenesis during Differentiation of 3T3-L1 preadipocytes . In addition, EAP decreased mRNA and protein levels of proliferator-activated receptor γ (PPARγ ) and CCAAT/enhancer-binding protein alpha (C/EBPα ). Moreover, EAP suppressed mRNA expressions of fatty acid synthase (FAS), lipoprotein lipase (LPL), Adipocyte protein 2 (aP2) in a dose-dependent manner. Whereas, EAP upregulated adiponectin expression, phosphorylation levels of AMPK and carnitine palmitoyltransferase 1 (CPT-1) protein level during Differentiation of 3T3-L1 preadipocytes.

These results suggest that EAP water extract can exert ROS-linked Anti-Obesity effect through the mechanism that might involve Inhibition of ROS production, Adipogenesis and lipogenesis via an activating AMPK signaling pathway.

Euphorbia lunulata

Syzygium aqueum leaf extract and its bioactive compounds enhances pre-Adipocyte Differentiation and 2-NBDG uptake in 3T3-L1 cells

The insulin-like and/or insulin-sensitising effects of Syzygium aqueum leaf extract and its six bioactive compounds; 4-hydroxybenzaldehyde, myricetin-3-O-rhamnoside, europetin-3-O-rhamnoside, phloretin, myrigalone-G and myrigalone-B were investigated in 3T3-L1 Adipocytes. We observed that, S. aqueum leaf extract (0.04–5 μg/ml) and its six bioactive compounds (0.08–10 μM) at non-cytotoxic concentrations were effectively enhance Adipogenesis, stimulate glucose uptake and increase adiponectin secretion in 3T3-L1 Adipocytes. Clearly, the compounds myricetin-3-O-rhamnoside and europetin-3-O-rhamnoside showed insulin-like and insulin-sensitising effects on Adipocytes from a concentration of 0.08 μM.

These compounds were far better than rosiglitazone and the other isolated compounds in enhancing Adipogenesis, stimulating 2-NBDG uptake and increasing adiponectin secretion at all the concentrations tested. These suggest the AntiDiabetic potential of S. aqueum leaf extract and its six bioactive compounds. However, further molecular interaction studies to explain the mechanisms of action are highly warranted.

Evodiamine (Evodia rutaecarpa)

Evodiamine Inhibits Adipogenesis via the EGFR–PKCα–ERK signaling pathway

The molecular mechanism of the Anti-Adipogenic effect of evodiamine (which has several capsaicin-like pharmacological actions) was investigated. The evodiamine effect was not blocked by the specific TRPV1 antagonist capsazepine in 3T3-L1 preadipocytes , whereas its effect was greatly curtailed by Inhibitors of protein kinase C (PKC) and epidermal growth factor receptor (EGFR). Signal analyses showed that evodiamine stimulated the phosphorylation of EGFR, PKCα, and ERK, all of which were Reduced by an Inhibitors EGFR Inhibitor.

Silencing experiments of EGFR mRNA supported the involvement of these signaling molecules in the Inhibitory effect of evodiamine. An unidentified mechanism whereby evodiamine Inhibits Adipogenesis via the EGFR–PKCα–ERK signaling pathway was revealed.

Ferulic Acid (Ferula assafoetida L)

Aqueous extracts of hulled barley containing coumaric acid and ferulic acid Inhibit Adipogenesis in vitro and Obesity in vivo

World epidemic Obesity is a major contributing factor to metabolic diseases including insulin resistance and cardiovascular diseases. In this study, aqueous and ethanolic extracts of hulled barley with roasting temperatures of up to 250 °C were investigated for their Anti-Adipogenic effects in vitro and in vivo. An aqueous extract of hulled barley roasted at 210 °C (AHB210) effectively Inhibited Adipocyte Differentiation. Intraperitoneal injections of 15 or 50 mg/kg AHB210 dose dependently prevented body Weight Gain, fat Mass increase, and dysregulated lipid profiles in high fat diet-induced obese male mice. In addition, oral administration of AHB210 to ovariectomized rats also prevented body Weight Gain.

A high performance liquid chromatographic analysis identified coumaric acid and ferulic acid as primary Anti-Obesity mediators. The presence of beta glucan in AHB210 was less likely to be responsible for the lipid accumulating actions. Taken together, AHB210 may be useful to Prevent Obesity and its related metabolic diseases.

Ficus deltoidea

Anti-Adipogenic effects of extracts of Ficus deltoidea var. deltoidea and var. angustifolia on 3T3-L1 Adipocytes

Objective: This study examined the Anti-Adipogenic effects of extracts of Ficus deltoidea var. deltoidia and var. angustifolia, a natural slimming aid, on 3T3-L1 Adipocytes.

Methods: Methanol and water extracts of leaves of the F. deltoidea varieties were analyzed to determine their total flavonoid content (TFC) and total phenolic content (TPC), respectively. The study was initiated by determining the maximum non-toxic dose (MNTD) of the methanol and water extracts for 3T3-L1 preadipocytes. Possible Anti-Adipogenic effects were then examined by treating 2-d post confluent 3T3-L1 preadipocytes with either methanol extract or water extract at MNTD and half MNTD (½MNTD), after which the preadipocytces were induced to form mature Adipocytes. Visualisation and quantification of lipid content in mature Adipocytes were carried out through oil red O staining and measurement of optical density (OD) at 520 nm, respectively.

Results: The TFCs of the methanol extracts were 1.36 and 1.97 g quercetin equivalents (QE)/100 g dry weight (DW), while the TPCs of the water extracts were 5.61 and 2.73 g gallic acid equivalents (GAE)/100 g DW for var. deltoidea and var. angustilofia, respectively. The MNTDs determined for methanol and water extracts were (300.0±28.3) and (225.0±21.2) µg/ml, respectively, for var. deltoidea, while much lower MNTDs [(60.0±2.0) µg/ml for methanol extracts and (8.0±1.0) µg/ml for water extracts] were recorded for var. angustifolia. Studies revealed that the methanol extracts of both varieties and the water extracts of var. angustifolia at either MNTD or ½MNTD significantly Inhibited the maturation of preadipocytes.

Conclusions: The Inhibition of the formation of mature Adipocytes indicated that leaf extracts of F. deltoidea could have potential Anti-Obesity effects.

fisetin (Cotinus Coggygria)

Inhibition of mitotic clonal expansion mediates fisetin-exerted prevention of Adipocyte Differentiation in 3T3-L1 cells

Adipocytes are the key player in Adipose Tissue Inflammation and subsequent systemic insulin resistance and its development involves complex process of proliferation and Differentiation of preadipocytes. Fistein, a Polyphenol flavonoid, is known to exert anti-inflammatory, anti-carcinogenic and anti-Diabetic effects. In this study, we aimed to investigate the effect of fisetin on Adipocyte proliferation and Differentiation in 3T3-L1 Preadipocyte cell line and its mechanism of action. We found that fisetin Inhibits Adipocyte Differentiation in a concentration dependent manner, which were evidenced by Oil Red O staining and the protein expression of mature Adipocyte marker genes fatty acid synthase and peroxisome proliferator-activated receptor γ.

Moreover, the proliferation of preadipocytes was also markedly suppressed by treatment of fisetin for 24 and 48 h in the Differentiation medium. We also found that fisetin Inhibition of Adipocyte Differentiation was largely due to the effect on mitotic clonal expansion. Fisetin suppression of Preadipocyte proliferation at early stage of Differentiation was accompanied by the changes of expression of a series of cell cycle regulatory proteins. Altogether, our results suggest that the Inhibition of Adipocyte Differentiation by fisetin may be at least in part mediated by cell cycle arrest during Adipogenesis.

Foenumoside B (Lysimachia foenum-graecum)

Foenumoside B from Lysimachia foenum–graecum Inhibits Adipocyte Differentiation and Obesity induced by high-fat diet

We have previously reported anti-obesity effects of Lysimachia foenum-graecum in high-fat diet (HFD)-induced obesity model. Here we isolated a triterpene saponin foenumoside B as an active component of L. foenum-graecum. Foenumoside B blocked the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner with an IC50 of 0.2 μg/ml in adipogenesis assay and suppressed the induction of PPARγ, the master regulator of adipogenesis. Foenumoside B induced the activation of AMP-activated protein kinase (AMPK), and modulated the expression of genes involved in lipid metabolism towards lipid breakdown in differentiated adipocytes. In mouse model, oral administration of foenumoside B (10mg/kg/day for 6 weeks) reduced HFD-induced body weight gain significantly without affecting food intake. Treatment of foenumoside B suppressed lipid accumulation in white adipose tissues and the liver, and lowered blood levels of glucose, triglycerides, ALT, and AST in HFD-induced obese mice.

Consistent with the in vitro results, foenumoside B activated AMPK signaling, suppressed the expression of lipogenic genes, and enhanced the expression of lipolytic genes in vivo. Foenumoside B also blocked HFD-induced proinflammatory cytokine production in adipose tissue, suggesting its protective role against insulin resistance. Taken together, these findings demonstrate that foenumoside B represents the anti-obesity effects of L. foenum-graecum, and suggest therapeutic potential of foenumoside B in obesity and obesity-related metabolic diseases.

fucoxanthin  

Fucoxanthin and its metabolite, fucoxanthinol, suppress Adipocyte Differentiation in 3T3-L1 cells

Fucoxanthin is a major carotenoid found in edible seaweed such as Undaria pinnatifida and Hijikia fusiformis. We investigated the suppressive effects of fucoxanthin and its metabolite, fucoxanthinol, on the differentiation of 3T3-L1 preadipocytes to adipocytes. Fucoxanthin inhibited intercellular lipid accumulation during adipocyte differentiation of 3T3-L1 cells. Furthermore, fucoxanthin was converted to fucoxanthinol in 3T3-L1 cells. Fucoxanthinol also exhibited suppressive effects on lipid accumulation and decreased glycerol-3-phosphate dehydrogenase activity, an indicator of adipocyte differentiation.

The suppressive effect of fucoxanthinol was stronger than that of fucoxanthin. In addition, in 3T3-L1 cells treated with fucoxanthin and fucoxanthinol, peroxisome proliferator-activated receptor gamma (PPARgamma), which regulates adipogenic gene expression, was down-regulated in a dose-dependent manner. These results suggest that fucoxanthin and fucoxanthinol inhibit the adipocyte differentiation of 3T3-L1 cells through down-regulation of PPARgamma. Fucoxanthinol had stronger suppressive effects than fucoxanthin on adipocyte differentiation in 3T3-L1 cells.

Gallotannin (Mangifera indica)

Gallotannin derivatives from mango (Mangifera indica L.) suppress Adipogenesis and increase thermogenesis in 3T3-L1 Adipocytes in part through the AMPK

Expansion of adipose tissue in obesity is associated with dysregulation of adipokines, which can lead to long-term metabolic disorders. Gallotannin derivatives from mango possess anti-inflammatory activities, but their potential role in lipid metabolism is not well investigated. In this study, 3T3-L1 preadipocytes were differentiated into adipocytes and treated with mango polyphenols (MG), or pyrogallol (PG) for 6 days. The anti-adipogenic activity of PG was demonstrated by reduced number of lipid droplets and expressions of adipogenic markers, such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα).

In mature adipocytes, PG promoted adipocyte browning and increased the expressions of uncoupling protein 1 (UCP1) and sirtuin 1 (Sirt1). Knockdown of AMP-activated protein kinase (AMPK) α1 with siRNA partially abolished the effect of PG on adipogenesis. Results indicate that gallotannin derivatives modulate lipid metabolism, at least in part, though the AMPK pathway, and possess potential to prevent obesity-related conditions.

Four new lanostane triterpenes, butyl ganoderate A, butyl ganoderate B, butyl lucidenate N, and butyl lucidenate A, were isolated from the fruiting bodies of Ganoderma lucidum together with 14 known compounds. The structures of the new triterpenes were established by extensive spectroscopic studies and chemical evidence. In addition, the Inhibitory effect of isolated compounds on Adipocyte Differentiation in 3T3-L1 cells was examined.

Altered Gelidium elegans Extract-stimulated Beige-like Phenotype Attenuates Adipogenesis in 3T3-L1 cells

Previously, we showed that Gelidium elegans extract (GE) Suppresses oxidative stress and lipid accumulation. However, the molecular mechanism underlying the Anti-Adipogenic ability of GE is still unclear. The levels of Adipogenesis markers and triglyceride synthesis enzymes were measured by western blot. To evaluate the lipid accumulation in 3T3-L1 cells, oil red o staining was performed. We investigated whether GE induces Lipolysis by measuring Adipocyte triglyceride lipase (ATGL) during Adipocyte Differentiation. We also examined the expression of beige cell-associated genes and the production of carbon dioxide in 3T3-L1 cells. We showed that GE increased the protein expression of CAAT/enhancer binding protein (C/EBP) homologous protein 10 and Inhibited the expression of C/EBPβ. GE discouraged triglyceride synthesis via deregulation of lysophosphatidic acid acyltransferase-θ (LPAATθ) and diacylglycerolacyltransferase 1 (DGAT1) during late-stage Adipogenesis in 3T3-L1 cells. GE also dramatically increased ATGL in 3T3-L1 cells.

Finally, in 3T3-L1 cells treated with GE, markers of beige Adipocytes such as PRDM16 and UCP1 were upregulated, and large amounts of carbon dioxide were produced. These data indicate that GE Suppresses Adipogenesis by stimulating a beige-like phenotype in 3T3-L1 cells.

Genistein

Gentiopicroside (Gentiana scabra)

Gentiopicroside isolated from Gentiana scabra Bge. Inhibits Adipogenesis in 3T3-L1 cells and Reduce s body weight in diet-induced obese mice

Ginkgetin (Ginkgo biloba)

Ginkgetin, a biflavone from Ginkgo biloba leaves, prevents Adipogenesis through STAT5-mediated PPARγ and C/EBPα regulation

Ginkgo Biloba

Ginkgetin, a biflavone from Ginkgo biloba leaves, prevents Adipogenesis through STAT5-mediated PPARγ and C/EBPα regulation

Adipogenesis involved in hypertrophy and hyperplasia of Adipocytes is responsible for expanding the Mass of Adipose Tissue s in obese individuals. Peroxisome proliferator-activated receptor γ (PPARγ ) and CCAAT/enhancer-binding protein α (C/EBPα ) are two principal transcription factors induced by delicate signaling pathways, including signal transducer and activator of transcription 5 (STAT5), in Adipogenesis. Here, we demonstrated a novel role of ginkgetin, a biflavone from Ginkgo biloba leaves, as a STAT5 Inhibit or that blocks the Differentiation of preadipocytes into Adipocytes.

During the Differentiation of 3T3-L1 cells, ginkgetin treatment during the first 2 days markedly Inhibited the formation of lipid-bearing Adipocytes . PPARγ and C/EBPα expression was decreased in 3T3-L1 cells during Adipogenesis following ginkgetin treatment, whereas no change was observed in C/EBPβ or C/EBPδ expression. Inhibition of PPARγ and C/EBPα expression by ginkgetin occurred through the prevention of STAT5 activation during the initiation phase of Adipogenesis. In addition, ginkgetin-mediated the Inhibition of Adipogenesis was recapitulated in the Differentiation of primary preadipocytes. Lastly, we confirmed the Inhibitory effects of ginkgetin on the hypertrophy of white Adipose Tissues from high-fat diet-fed mice. These results indicate that ginkgetin is a potential anti-Adipogenesis and Anti-Obesity drug.

Ginsenoside Rg1, Rg2, Rg3

AntiObesity effects of ginsenoside Rg1 on 3T3-L1 preadipocytes and high fat diet-induced obese mice mediated by AMPK

Rg1 exhibits an Anti-Adipogenic effect via regulation of the expression of the transcriptional factors and lipid metabolism-related genes in vivo and in vitro. We observed that Rg1 administration significantly increased the phosphorylation level of AMP-activated protein kinase (AMPK) in both epididymal white Adipose Tissue and 3T3-L1 cells. These results indicated that Rg1 works both in an Anti-Adipogenic and Anti-Obesity manner through inducing AMPK activation, Inhibiting lipogenesis, and decreasing intracellular lipid content, Adipocyte size, and adipose weight.

Ginsenoside Rg2 Inhibits Adipogenesis in 3T3-L1 preadipocytes and Suppresses Obesity in high-fat-diet-induced obese mice through the AMPK pathway

Anti–Adipogenic effects and mechanisms of ginsenoside Rg3 in Pre-Adipocytes and obese mice

Red or black ginseng has been reported more powerful than white/fresh ginseng in dealing with various diseases/conditions including Obesity. The major reason is that heating/steaming, the process of making red or black ginseng, produces large amount of bioactive compounds including ginsenoside Rg3 (Rg3), which are trace in fresh or white ginseng. In the present study, Rg3 was applied both in Pre-Adipocytes and obese mice to investigate the Anti-Adipogenic effects and relevant mechanisms. Our results show that Rg3 dose-dependently Inhibited cell Differentiation both in 3T3-L1 cells (30, 50, and 100 μM) and human primary Pre-Adipocytes (10, 20, and 30 μM).

This Inhibitory effect is accompanied by the attenuation of the expressions of Adipogenic markers including peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein alpha (C/EBP-α), fatty acid synthase (FAS), fatty acid binding protein 4 (FABP4) and perilipin. Although dietary intake of Rg3 (0.1 mg Rg3/kg diet, 8 weeks) did not significantly affect body Weight Gain , fat pads and food intake as well as of PPAR-γ expression in fat tissues, we found that hepatic PPAR-γ and C/EBP-α protein expressions and hepatic glutathione reductase and glutathione S-transferase, two major Antioxidants molecules were significantly Reduced by Rg3. These results suggest that ginsenoside Rg3 may be a potential agent in reducing/preventing Obesity.

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AntiObesity effect of ginsenoside Rg3 involves the AMPK and PPAR‐γ signal pathways

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Ginsenosides, the active component of ginseng, exerts AntiDiabetic and anticancer effects. This study investigated the molecular basis of ginsenoside Rg3, a red ginseng rich constituent, focusing on its ability to Inhibit Adipocyte Differentiation in 3T3‐L1 cells. The data show that ginsenoside Rg3 was effective in the Inhibition of Adipocyte Differentiation.

This Inhibitory effect of ginsenoside Rg3 on Adipocyte Differentiation was accompanied by PPAR‐γ Inhibition in rosiglitazone‐treated cells. The study also tested whether AMP‐activated protein kinase (AMPK) activation was involved in the Inhibitory effects of ginsenoside Rg3. AMPK plays a role in maintaining health in the context of diseases such as type 2 Diabetes, Obesity and cancer. AMPK was reported to control nutritional and hormonal signal modulating. Rg3 significantly and time‐dependently activated AMPK. Taken together, these results suggest that the AntiObesity effect of red ginseng rich constituent, ginsenoside Rg3, involves the AMPK signaling pathway and PPAR‐γ Inhibition.

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Ginsenoside Rg3 ameliorated HFD-induced hepatic steatosis through downregulation of STAT5-PPARγ

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The LC₅₀ value of Rg3 in 3T3-L1 cell lipogenesis is 200 μM, and our working concentrations (5, 25 and 50 μM) of Rg3 Reduced lipogenesis without cell toxicity (Fig. 1B and C). To investigate the Inhibiting effect on lipid accumulation by Rg3, we treated 3T3-L1 cells for 3 or 9 days. Oil Red O staining confirmed lipid accumulation in the cell. At 3 days, the lipogenic cocktail MDI (insulin, dexamethasone and isobutylmethylxanthine) induced in Pre-Adipocytes a very low increase in their accumulated fat deposits. When Rg3 was combined with MDI-induced cells, their lipid accumulation was suppressed (Fig. 1D), in an Rg3 dose-dependent manner, as assessed at 9 days after treatment using Oil Red O staining microscopy data and Oil Red O absorbance at 520 nm (Fig. 1E). In Adipocytes, lipid accumulation is related to the amount of TGs in the cell. Similar to the Oil Red O staining results, TG storage was Reduced by Rg3 treatment in 3T3-L1 cells in a dose-dependent manner (Fig. 1F). These data suggest that Rg3 can Prevent lipogenesis and lipid accumulation in the 3T3-L1 cell line.

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Ginsenoside Rg3 induces browning of 3T3-L1 Adipocytes by activating AMPK signaling

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Rg3 induced the expression of beige fat-specific genes (CD137 and TMEM26) and lipid metabolism-associated genes (FASN, SREBP1, and MCAD), which indicated the activation of lipid metabolism by Rg3. We also demonstrated that activation of 5’ adenosine monophosphate-activated protein kinase (AMPK) is required for Rg3-mediated up-regulation of browning gene expression. Moreover, Rg3 Inhibited the accumulation of lipid droplets and Reduced the droplet size in mature 3T3-L1 Adipocytes.

Taken together, this study identifies a novel role of Rg3 in browning of white Adipocytes, as well as suggesting a potential mechanism of an Anti-Obesity effect of Panax ginseng.

 

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Glehnia littoralis Root

Glehnia littoralis root extract Inhibits Fat Accumulation in 3T3-L1 cells and high-fat diet-induced obese mice by downregulating Adipogenic gene expression

Guarana (Paullinia cupana) is a plant originated in Brazil that presents a beneficial effect on body weight control and metabolic alterations. The aim of this study was to evaluate the effects of guarana on genes and miRNAs related to Adipogenesis in 3T3L1 cells. The Anti-Adipogenic effect of guarana was evaluated by Oil Red-O staining. Gene and miRNA expression levels were determined by real time PCR. The Cebpα and β-catenin nuclear translocation were evaluated using immunocytochemistry. Our data indicated that the triglyceride-reducing effect of guarana was dose-dependent from 100 to 300 µg/mL (−12%, −20%, −24% and −40%, respectively, p < 0.0001). An up-regulation of the Anti-Adipogenic genes Wnt10b, Wnt3a, Wnt1, Gata3 and Dlk1 and a down-regulation of Pro-Adipogenic genes Cebpα, PPARγ and Creb1 were also observed. Furthermore, guarana repressed mmu-miR-27b-3p, mmu-miR-34b-5p and mmu-miR-760-5p, that contributed for up-regulation of their molecular targets Wnt3a, Wnt1 and Wnt10b.

We explored the potential of hesperidin and capsaicin, separately and in combination, to induce white Adipose Tissue (WAT) browning and to help body weight management in Western diet-fed rats. Adult male Wistar rats were fed for 8 weeks with Western diet and treated daily with hesperidin (100 mg/kg/day), capsaicin (4 mg/kg/day), hesperidin (100 mg/kg/day) + capsaicin (4 mg/kg/day), or the vehicle. Hesperidin and capsaicin separately, but not (or to a lesser extent) the combination, resulted in a decreased size of Adipocytes and induced emergence of multilocular brown-like Adipocytes positive for UCP1 and CIDEA in retroperitoneal WAT.

Expression levels of browning markers, such as Prdm16, in inguinal WAT also increased with capsaicin treatment compared with the vehicle (145% ± 17% vs 92% ± 21%, P < 0.05), but no significant effects were found with the combination (106% ± 12%). Thus, the combination of both bioactives Reduces the effectiveness of each compound to decrease the Adipocyte size and induce WAT browning.

Hibiscus rosa sinensis flower

AMPK activating and anti Adipogenic potential of Hibiscus rosa sinensis flower in 3T3-L1 cells

Hibiscus sabdariffa L

Beneficial effects of natural bioactive compounds from Hibiscus sabdariffa L. on Obesity

This review has gathered reports on the various anti-obesity effects of H. sabdariffa bioactive compounds in cell and animal models, as well as in humans. Available toxicology information on the consumption of H. sabdariffa revealed that its toxicity is dose-dependent and may cause an adverse effect when administered over a long period of time. Reports have shown that H. sabdariffa derived