FEATURING: A. VENETUM L. • ACHILLEA • AGASTACHE MEXICANA • ALISMA ORIENTALIS(SAM.)JUZEP. • ALLIUM SATIVUM • ANTRODIA CAMPHORATA • ARONIA MITCHURINII • ARTEMISIA HERBA ALBA • ARTEMISIA SCOPARZA WALDST.ET KIT • ASTRAGALUS COMPLANATUS • ASTRAGALUS MEMBRANACEUS • AVERRHOA ARAMBOLA • BORAGO OFFICINALIS • BUDDLEJA CRISPA • CALYCOTOME VILLOSA • CAROM CAPTICUM • CARTHAMUS TINCTORIUS L. • CASSIA SEED • CATHARANTHUS ROSEUS • CECROPIA PACHYSTACHYA • CIRSIUM JAPONICUM • CITRUS LIMETTA • CLERODENDRON TRICHOTOMUM • COCOS NUCIFERA • COPTIS CHINENSIS FRANCH • CORIANDRUM SATIVUM • COSCINIUM FENESTRATUM • CRATAEGUS PINNATIFIDA BUNGE • CROCUS SATIVUS • CUDRANIA TRICUSPIDATA • CUSCUTA JAPONICA • ECHINODORUS GRANDIFLORUS • EKEBERGIA CAPENSIS • ELETTARIA CARDAMOMUM • EPIMEDIUM BREVICORNUM MAXIM. • ERRACHIDIA PROVINCE • EUCOMMIA ULMOIDES OLIVER • EUGENIA UNIFLORA • EUODIA RUTAECARPA (JUSS.)BENT • FICUS DELTOIDEA VAR. KUNSTLERI • FICUS EXASPERATE • FRITILLARIA USSURIENSIS MAXIM • GANODERMA LUCIDUM SPORE POWDER • GASTRODIA ELATA BL • GASTRODIA ELATA BLUME • GEUM JAPONICUM • GINKGO BILOBA L. • GLOBIMETULA CUPULATA • GRAPTOPETALUM PARAGUAYENSE • GUAZUMA ULMIFOLIA • GYNURA PROCUMBENS • HALIOTIDIS CONCHA • HARPEPHYLLUM CAFFRUM BERNH • HIBISCUS SABDARIFFA • HORDEURN VULGARE L • HYPTIS FRUTICOSA • JACARANDA MIMOSAEFOLIA • JATROPHA GOSSYPIIFOLIA • LAELIA ANCEPS • LAELIA AUTUMNALIS • LAMINARIA JAPONICA ARESCH. • LEONURUS JAPONICUS HOUTT • LEPECHINIA CAULESCENS • LEPIDIUM SATIVUM • LILIUM LANCIFOLIUM THUNB. • LORANTHUS FERRUGINEUS • LYCIUM BARBARUM L. • LYCIUM CHINENSE MILL. • LYCOPUS LUCIDUS TURCZ.VAT.HIRTUS REGEL • MADERASPATANA • MELOTHRIA • MOMORDICA CHARANTIA • MONASCUS PURPUREUS WENT. • NIGELLA SATIVA • OENOTHERA BIENNIS • OPHIOPOGON JAPONICUS (LINN. F.) KER-GAWL. • PANAX GINSENG • PANAX GINSENG C. A. MEYER • PANAX PSEUDO-GINSENG • PASSIFLORA EDULIS RIND • PERIPLOCA LAEVIGATA • PERSEA AMERICANA MILL • PHYLLANTHUS ACIDUS • PHYLLANTHUS URINARIA • PINELLIA TERNATA( THUNB.) BREIT • PLEUROTUS NEBRODENSIS • POLYALTHIA LONGIFOLIA • POLYGONUM CUSPIDATUM SIEB.ET ZUCC. • PRUNELLA VULGARIS L. • PUERARIA LOBATA (WILLD.) OHWI • RADIX BUPLEURI • RAPHANUS SATIVUS • REHMANNIA GLUTINOSA (GAETN.) LIBOSCH. EX FISCH. ET MEY • RETAMA RAETAM FORSSK • RHEUM PALMATUM L． • SALVIA CINNABARINA • SALVIA MILTIORRHIZA BGE • SAURURUS CHINENSIS • SCHISANDRA CHINENSIS • SCLEROCARYA BIRREA • SCROPHULARIAE RADIX • SCUTELLARIAE RADIX • SIEGESBECKIA ORIENTALIS L. • SOLANUM TORVUM • SOPHORA JAPONICA L. • TANACETUM VULGARE • TRIBULUS TERRESTRIS • TROPAEOLUM MAJUS • UNCARIA RHYNCHOPHYLLA • VALERIANA WALLICHII
SCIENCE & INGREDIENTS:
A. venetum L.
Effects of aqueous extracts of Apocynum venetum leaves (Luobuma extracts) on the blood pressure were evaluated in hypertensive animal models, such as spontaneously hypertensive rats (SHR), renal hypertensive rats and NaCl-induced hypertensive rats. In SHR, administration of Luobuma (heat-processed and unprocessed leaves) extracts at a dose of 70 mg/rat per day significantly decreased the systolic blood pressure value, but their decreasing effects were weaker than that of captopril. The urine volume, and the urinary Na+, K+ and protein excretions were not significantly different between Luobuma-treated and untreated groups. In 3/4 nephrectomized rats, the Luobuma extracts significantly decreased the systolic blood pressure value, accompanied by significant increases of the urine volume and the urinary Na+ and K+ excretions. Furthermore, they decreased the blood urea nitrogen (BUN) level. In NaCl-induced hypertensive rats, the Luobuma extract decreased the systolic blood pressure value. However, it did not change the urinary excretions of Na+, K+ and protein. The BUN level was lower than that of control rats, but the serum total cholesterol (TC) level did not changed. From these findings, the Luobuma extracts have an anti-hypertensive effect, possibly due to amelioration of the kidney functions in the three experimental animal models.
Traditional uses of Achillea millefolium L. (Asteraceae) include the treatment of cardiovascular diseases. In the present study, we used anesthetized rats to assess the hypotensive effect of a hydroethanolic extract (HEAM), and its dichloromethane (DCM), ethyl acetate (EA), butanolic (BT), and dichloromethane-2 (DCM-2) fractions, besides the ﬂavonoid artemetin, isolated from A. millefolium. The oral administra- tion of HEAM (100–300 mg/kg), DCM (20 mg/kg), DCM-2 (10–30 mg/kg), but not EA (10 mg/kg) and BT (50 mg/kg) fractions signiﬁcantly reduced the mean arterial pressure (MAP) of normotensive rats. The phytochemical analysis by NMR 1H of DCM and DCM-2 fractions revealed high amounts of artemetin, that was isolated and administered by either oral (1.5 mg/kg) or intravenous (0.15–1.5 mg/kg) routes in rats. This ﬂavonoid was able to dose-dependently reduce the MAP, up to 11.47 ± 1.5 mm Hg (1.5 mg/kg, i.v.). To investigate if artemetin-induced hypotension was related to angiotensin-converting enzyme inhibition, we evaluated the inﬂuence of this ﬂavonoid on the vascular effects of both angiotensin I and bradykinin. Intravenous injection of artemetin (0.75 mg/kg) signiﬁcantly reduced the hyperten- sive response to angiotensin I while increased the average length of bradykinin-induced hypotension. Artemetin (1.5 mg/kg, p.o.) was also able to reduce plasma (about 37%) and vascular (up to 63%) ACE activity in vitro, compared to control group. On the other hand, artemetin did not change angiotensin II-induced hypertension. Our study is the ﬁrst showing the hypotensive effects induced by the extract and fractions obtained from A. millefollium. In addition, our results disclosed that this effect may be, at least in part, associated with high levels of artemetin and its ability to decrease angiotensin II generation in vivo, by ACE inhibition.
Current investigation was undertaken to elucidate the mode of action of tilianin, isolated from Agastache mexicana, as a vasorelaxant agent on in vitro functional rat thoracic aorta test and to investigate the in vivo antihypertensive effect on spontaneously hypertensive rats (SHR). Tilianin (0.002-933 microM) induced significant relaxation in a concentration- and endothelium-dependent and -independent manners in aortic rings pre-contracted with noradrenaline (NA, 0.1 microM), and serotonin (5-HT, 100 microM). Effect was more significant (p < 0.05) in endothelium-intact (+E) aorta rings than when endothelium was removed(E). Pre-treatment with N-nitro-L-arginine methyl ester (L-NAME; 10 microM) or 1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (ODQ, 1 microM) produced a significant change of the relaxant response and activity was markedly inhibited, but not by indomethacin (10 microM) or atropine (1 microM). Furthermore, tilianin (130 microM) provoked a significant displacement to the left in the relaxation curve induced by sodium nitroprusside (SNP; 0.32 nM to 0.1 microM). Moreover, tilianin induced significant in vitro NO overproduction (1.49 +/- 0.86 microM of nitrites/g of tissue) in rat aorta compared with vehicle (p < 0.05). In addition, pre-treatment with tetraethylammonium (TEA, 5 mM) and 2-aminopyridine (2-AP, 0.1 microM) shifted to the right the relaxant curve induced by tilianin (p < 0.05). Finally, a single oral administration of tilianin (50 mg/kg) exhibited a significant decrease in systolic and diastolic blood pressures (p < 0.05) in SHR model. Results indicate that tilianin mediates relaxation mainly by an endothelium-dependent manner,probably due to NO release, and also through an endothelium-independent pathway by opening K+ channels, both causing the antihypertensive effect.
Diabetic nephropathy (DN) is the leading cause of the end-stage failure of kidney, but the efficacy of currently available strategies for the prevention of DN remains poor. An activation of the transcription factor, nuclear factor-κB (NF-κB), has been suggested to be a key step in the pathogenesis of DN. In the present study, we investigated the effect of Astragalus polysaccharide (APS), an aqueous extract from the Astragalus membranaceus roots, on gene expressions of NF-κB and an inhibitory protein of nuclear factor-κB (IκB) in experimental DN induced by streptozotocin in male Sprague-Dawley rats.
Rats with DN were treated with APS (1 g/kg p.o.) or benazepril (1.5 mg/kg p.o.), an angiotensin-converting enzyme inhibitor, using as positive control. The biochemical parameters such as blood glucose, plasma lipid and microalbuminuria were measured. Also, the mRNA level of NF-κB or IκB in renal cortex was determined using reverse transcription-polymerase chain reaction.
Eight weeks after the treatment, symptoms including shineless, bristly hair, polyuria, polydipsia, lethargy, physical inactivity, loss of body weight, kyphosis and decubitus position were ameliorated by APS. The levels of blood glucose, plasma lipid and microalbuminuria were lowered in APS-treated rats compared with control rats. The ratio of kidney weight over body weight was reduced and the renal function was improved after APS treatment. The mRNA level of NF-κB in renal cortex was decreased and IκB mRNA expression was raised by APS. These results suggest that APS has prophylactic and therapeutic effects on the progress of DN;
therefore, APS is helpful for the prevention and/or treatment of DN at early stage.
Oryeongsan (ORS, Wulingsan), a formula composed of five herbal medicines, has long been used for the treatment of impairments of the regulation of body fluid homeostasis in China, Japan and Korea.
Aim of the study
The purpose of the present study was to test the effects of ORS on the renal function and the mechanisms involved in rats.
Materials and methods
Experiments were performed in rats caged individually. Renal function and plasma levels of renin activity and aldosterone concentration were measured.
Treatment of ORS resulted in increases in urinary volume, excretion of Na+, K+, and Cl−, and glomerular filtration rate, and decreases in urinary osmolality and Na+ balance. Further, ORS decreased plasma renin activity and aldosterone concentration. An increase in urinay excretion of Na+ was a function of glomerular filtration rate, while the increase in the day-time period was related with the increase in the ratio of urinary Na+/K+.
Therefore, the present results suggest that ORS induces diuresis and natriuresis via inhibition of the renin–angiotensin–aldosterone system in rats.
The rennin-angiotensin system (RAS) has been implicated in the development of diabetic vascular complications. Peptidyl-dipeptidase A (angiotensin converting enzyme, ACE) has a major role in this system. The aim of the present study was to clarify the effect of intraperitoneal administration of aqueous garlic extract (Allium sativum) on the serum ACE activity of streptozotocin (STZ)-diabetic and nondiabetic rats. Although garlic extract administration had no significant effect on serum glucose, it significantly strongly decreased the serum ACE activity. ACE activity was higher in diabetic than nondiabetic rats, but in diabetic animals treated with garlic extract, the elevation of ACE activity did not occur. These results suggest that garlic extract might have value as ACE inhibitor to prevent some vascular complications of diabetes mellitus.
Antrodia camphorata, a medicinal fungus, has been used to treat cardiovascular diseases such as hypertension for many years. The purpose of this study was to examine the effects of mycelia extracts, from five Antrodia camphorata strains, on vascular tension and underlying mechanisms were explored. In isolated rat aortic rings, accession B86 caused concentration-dependent vasorelaxation with maximal relaxation of 40.34 +/- 7.53% whereas accessions 35398, 35396 and B71 had mild vasorelaxing effects. Strain B85 evoked potent vasorelaxation, partly through an endothelium-dependent mechanism that was inhibited by Nomega-nitro-L-arginine and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) but not by antagonist of K+ channels, tetraethylammonium. In cultured endothelial cells, B85 stimulated nitric oxide (NO) release and augmented the level of the intracellular Ca2+ concentration. HPLC and LC-MS-MS analysis revealed the presence of adenosine. Our results suggest that B85 produced strongest vasorelaxation in aortic preparations among five test strains. B85 acts in part on endothelial cells by activating the Ca(2+)-NO-cGMP pathway to reduce smooth muscle tone. However, K+ channels had no apparent roles. Adenosine could possibly be involved in the endothelium-dependent pathway of B85-induced vasorelaxation.
The blood pressure-lowering properties of lyophilized chokeberry juice and polyphenols were monitored using in vitro angiotensin-converting enzyme (ACE) inhibition measurement and a 10day in vivo study with spontaneously hypertensive rats (SHR). Juice and polyphenols indicated weak ACE-inhibitory activity. The IC 50 values for polyphenols and juice were 1.5–2.5 and 4.5mg dry matter/ml, respectively. In the SHR study the blood pressure-lowering effects of juice and polyphenol extract seemed to be short-term and were generally highest after 3h from administration (50mg/kg/day) when mean reductions in systolic blood pressure were 20±8 and 15±7mmHg, respectively. Corresponding mean decreases in diastolic blood pressure were 23±6 and 13±2mm Hg in juice and polyphenol groups, respectively. It was concluded that both chokeberry juice and polyphenols had blood pressure-lowering effects. We hypothesize that chokeberry polyphenols enhance endothelial nitric oxide production with an ACE-independent mechanism, e.g. by activation of endothelial nitric oxidase enzyme; this is yet to be verified.
Artemisia herba alba
This study aimed to evaluate the hypotensive activity of Artemisia herba alba aqueous extract (AHAE) in spontaneously hypertensive rats (SHR). AHAE was lyophilized and administered daily at a dose of 150 mg/kg for 20 days. AHAE administration produced a significant reduction in systolic blood pressure after 8 days of oral administration (P < 0.01), and a sustained reduction was observed at the end of treatment (P < 0.01). Heart rate remained unchanged during the 20 days of oral AHAE administration. In addition, AHAE administration produced a significant increase in urinary output (P < 0.01) and glomerular filtration rate (P < 0.01) on day 8 of treatment. Urinary electrolyte excretion was also modified during the 20 days of AHAE administration, and a significant increase in urinary sodium and potassium excretion was observed from day 4 (P < 0.01) to day 20 (P < 0.001). However, urinary chloride excretion was increased from day 8 (P < 0.01) to the end of treatment (P < 0.001). The hypotensive effect appeared to be independent of the renin–angiotensin system since AHAE did not affect plasma angiotensin-converting enzyme or renin activities (P > 0.05) after 20 days of oral administration. We conclude that AHAE possesses antihypertensive activity in SHR and that the underlying mechanism appears to involve, at least in part, an increase in urine and electrolyte output.
The objective of the present study was to examine further the underlying mechanism of the antihypertensive effect of the total flavonoid (TF), extracted from the seed of Astragalus complanatus R.Brown. Renovascular hypertension rats (RHR) were established by the two-kidney one clip (2K1C) method. The effect of TF on the contraction of portal vein was studied in an isolated preparation. The response of portal vein to angiotensin II (Ang II) was expressed as a percentage of the 100 mmol/l KCl induced maximum contraction. We took the dose-response curve of portal vein to Ang II (from 10(-9) to 10(-6) mmol/l) as the control and then observed the change of curve after TF and Valsartan (Ang II receptor blocker) administration. Ang II induced a concentration-dependent increase of the contraction amplitude (maximal increase, 46.53+/-5.15% of 100 mmol/l KCl induced contraction at Ang II 10(-6) mmol/l in RHR). The Ang II-induced portal vein contraction was prevented by TF with a concentration related manner (maximal inhibition amplitude from 46.53+/-5.15% to 22.525+/-4.67% of 100 mmol/l KCl contraction at 10(-6)mmol/l Ang II and 3.12 x 10(-1) mg/l TF in RHR). The effect of TF on Ang II-induced portal vein contraction was similar to Valsartan. These results showed that the antihypertensive action of TF was attributed to the dilation of vessels and is related to the blockade of the Ang II receptor.
Artemisia scoparza Waldst.et Kit
We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic and diastolic blood pressure levels than the control group. The AS group also had lower angiotensin I converting enzyme (ACE) activity and angiotensin II content in serum compared to the control group. The AS group showed higher vascular endothelial growth factor and lower ras homolog gene family member A expression levels in kidney compared to the control group. The AS group had significantly lower levels of plasma lipid oxidation and protein carbonyls than the control group. One new and six known compounds were isolated from AS by guided purification. The new compound was determined to be 4′-O-β-D-glucopyranoyl (E)-4-hydroxy-3-methylbut-2-enyl benzoate, based on its nuclear magnetic resonance and electrospray ionization-mass spectroscopy data.
Aim of the study: In this study, we investigated the crude extract of Borago officinalis leaves (Bo.Cr) for its antispasmodic, bronchodilator, vasodilator and cardio-depressant activities to rationalize some of the traditional uses.
Materials and methods: Bo.Cr was studied using different isolated tissue preparations including rabbit jejunum, trachea, aorta, and guinea-pig atria.
Results: Bo.Cr which was tested positive for flavonoids, coumarins, sterols and tannins produced a concentration-dependent relaxation of spontaneous and K+ (80mM)-induced contractions in isolated rabbit jejunum preparations, suggestive of Ca++ antagonist effect, which was confirmed when pretreatment of the tissue with Bo.Cr produced a rightward shift in the Ca++ concentration-response curves like that caused by verapamil. In rabbit tracheal preparations, Bo.Cr relaxed the carbachol (1microM) and K+-induced contractions. Verapamil also produced non-specific inhibitory effect. In rabbit aorta preparations, Bo.Cr exhibited vasodilator effect against phenylephrine and K+-induced contractions similar to verapamil. When tested in guinea-pig atria, Bo.Cr caused inhibition of both atrial force and rate of contractions.
Conclusions: These results suggest that the spasmolytic effects of Bo.Cr are mediated possibly through Ca++ antagonist mechanism, which might explain the traditional use of Borago officinalis in hyperactive gastrointestinal, respiratory and cardiovascular disorders.
This aim of this study was to investigate the crude extract of Buddleja crispa (Bc.Cr) and its active constituent(s) for their antihypertensive and antispasmodic activities. The Bc.Cr caused a dose-dependent (3-10 mg/kg) fall in mean arterial pressure in rats under anesthesia. In rabbit aorta preparations, Bc.Cr (0.03-1 mg/mL) caused inhibition of high K(+) (80 mM) precontractions. The Bc.Cr (0.03-1 mg/mL) also inhibited spontaneous and high K(+) precontractions in rabbit jejunum preparations, suggestive of calcium channel blocking (CCB) activity. CCB activity was further confirmed when pretreatment of the tissues with Bc.Cr (0.03-0.10 mg/mL) caused a rightward shift in Ca(++) concentration response curves, similar to verapamil. Among the pure compounds, BdI-H3 was more potent against the high K(+) than spontaneous contractions and was around eight times more potent than Bc.Cr against the spontaneous contractions while the other two compounds, BdI-2 and BH-3 were inactive. Activity-directed fractionation revealed that the hexane fraction was more potent against K(+) precontractions. These data indicate that Bc.Cr possesses a blood-pressure lowering effect, mediated possibly through CCB, though additional mechanism(s) cannot be ruled out. Among the pure compounds, Bdl-H3 is likely to be the active compound involved in the spasmolytic and possibly BP lowering effect of the parent crude extract.
To assess the putative diuretic and antioxidant properties of Cassia occidentalis (C. occidentalis) leaves’ aqueous extract.
Adult rats were administered with C. occidentalis leaves aqueous extract acutely (24 h) and subchronically (7 d), at doses 80, 160, 240, 320, and 400 mg/kg (per os). Negative control group received only an equivalent volume of distilled water, while the two positive control groups received the diuretic drugs furosemide (20 mg/kg, ip.) and hydrochlorothiazide (HCTZ) (20 mg/kg, ip.). Urinary elimination of electrolytes in response to treatments was evaluated, together with changes in concentrations of creatinine, urea, aldosterone, glucose, and albumin in urine and plasma. Various urinary indicators of kidney function and plasmatic markers of oxidative stress were also assessed.
The acute administration of C. occidentalis increased the urinary excretion of 107.58% at the higher dose tested, compared to negative control. The reference drugs furosemide and HCTZ induced increases of 84.27% and 48.05%, respectively. Acutely, the extract induced Na+ and Cl− elimination, whereas subchronically an increase in K+ elimination was also observed. The extract also improved the kidney function indexes and oxidative stress markers. These effects were dose-dependent and comparable with positive control observations.
Our findings strongly suggest that C. occidentalis aqueous extract has diuretic and antioxidant activities, and deserves further studies considering the potential for the treatment of hypertension.
The present study was undertaken in normotensive anaesthetized male rats that received a continuous perfusionof a chrysin glucoside isolated from the flowers and leaves of Calycotome villosa subsp intermedia at a doseof 2.5 mg/kg, or furosemide (control diuretic) at a dose of 0.5 mg/kg. Compared with the control rats receivingNaCl (0.9%), the urine flow, glomerular filtration and electrolyte excretion (Na+++++, K+++++) increased significantlyin rats treated with chrysin glucoside (p<<<<< 0.001). A similar effect was observed in the rats perfused withfurosemide. Intravenous injections of bolus doses (1– 3 mg/kg) of the chrysin glucoside to anaesthetized ratselicited an immediate and dose-dependent decrease in mean arterial blood pressure (MABP). Pretreatmentof the rats with the nitric oxide synthase inhibitor, L-NOArg (10 mg/kg), reduced partially, but significantly(p<<<<< 0.01), the maximal decrease in MABP elicited by chrysin glucoside. In the rat isolated aorta prepara-tion, chrysin glucoside (10 –100μμμμμM) inhibited in a concentration-dependent manner the noradrenaline (1μμμμμM)induced contractions (IC50===== 52μμμμμM). This relaxant activity of chrysin glucoside was significantly reduced byincubation of the endothelium-intact rings with L-NOArg (100μμμμμM), (80 ±±±±± 4.7% vs 48 ±±±±± 5.06% in the absenceof L-NOArg). In conclusion, these results demonstrate a diuretic and hypotensive action of a chrysin glucosidefrom Calycotome villosa in anaesthetized rats and indicating an action on renal function, and an activevascular relaxation mediated partially through nitric oxide release.
Carthamus tinctorius L.
Metabolic syndrome, such as diabetes mellitus, obesity, atherosclerosis, and high blood pressure (HBP), are closely linked pathophysiologically. However, current monotherapies for metabolic syndrome fail to target the multifactorial pathology via multiple mechanisms, as well as resolving the dysfunctionality of the cells and organs of the body. We aimed to provide a comprehensive and up-to-date review of the pharmacological advances, therapeutic potential, and phytochemistry of Salvia miltiorrhiza, Carthamus tinctorius, and Danhong injection (DHI). We discussed the molecular mechanisms of the bioactive constituents relating to diabetes mellitus and metabolic disease for further research and drug development. Interestingly, Salvia miltiorrhiza, Carthamus tinctorius, and DHI have anti-inflammatory, anti-glycemic, anti-thrombotic, and anti-cancer properties; and they mainly act by targeting the dysfunctional vasculatures including the inflammatory components of the disease to provide vascular repair as well as resolving oxidative stress. The major bioactive chemical constituents of these plants include polyphenolic acids, diterpene compounds, carthamin, and hydroxysafflor yellow A. Treatment of diabetes mellitus and its associated cardiovascular complication requires a comprehensive approach involving the use of appropriate traditional Chinese medicine formula. Danshen, Honghua, and DHI target the multiple risk factors regulating the physiologic function of the body and restore normalcy, apart from the traditional advice on exercise and diet control as treatment options in a metabolic syndrome patient.
Coptis chinensis Franch
Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling
Left ventricular hypertrophy (LVH) is an important characteristic of hypertensive heart disease. Renin-angiotensin system (RAS) blockers have been shown to be effective drugs for the reversal of LVH. Clinical and experimental studies have shown that Zi Shen Huo Luo Formula (ZSHLF) can improve the efficacy of perindopril in the treatment of hypertensive LVH, but its mechanism is unclear. This study aimed to investigate the possible mechanism to improve the efficacy of perindopril. First, we identified 23 compounds in ZSHLF by ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis, among which ferulic acid, caffeic acid, vanillic acid, berberine, rutin, quercetin, kaempferol, stachydrine, and tiliroside have been reported to reduce blood pressure and exhibit cardioprotective effects. Second, we treated spontaneously hypertensive rats (SHRs) with perindopril and ZSHLF for 12 continuous weeks and found that chronic use of perindopril could increase the aldosterone (ALD) levels and cause aldosterone breakthrough (ABT). ZSHLF combined with perindopril reduced the ALD levels, interfered with ABT, decreased blood pressure, improved left ventricular diastolic dysfunction, and decreased the collagen volume fraction; these effects were superior to those of perindopril alone. In vitro experiments, ALD-induced cardiomyocytes (H9c2 cells) and cardiac fibroblasts were treated with ZSHLF-containing serum, which suppressed ALD-induced cardiomyocyte hypertrophy and cardiac fibroblast proliferation, increased mineralocorticoid receptor (MR) and Cav-1 colocalization and decreased phosphorylated epidermal growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase (pERK) protein expression the cells. In conclusion, ZSHLF can interfere with ABT and affect the pathological role of ALD by affecting MR and Cav-1 interactions and EGFR/ERK signaling pathway. These effects represent a possible mechanism by which ZSHLF improves the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive LVH treatment. However, the major bioactive components or metabolites responsible for the effects and the implications of these findings in patients need further verification.
The leaves extract of Catharanthus roseus was investigated for hypotensive and hypolipidemic effects in adrenaline-induced hypertensive rats (AIHR) and compared with those of Atenolol in a crossover design. The pharmacologically Active components responsible for hypotensive activities were isolated from plant using bioassay guided purification approach and the structure of the compounds was proposed by spectroscopic methods. Catharanthus roseus leaves extract and commercial drug Atenolol were administered through intraperitoneal (i.p) route for one week. Different biochemical parameters such as heart weight, blood glucose level, serum cholesterol level, serum triglyceride level, body weight and the relationships between them were measured. Catharanthus roseus leaves extract at a dose of 30 mg/155+/-15 gm of body weight was injected in rat at every morning during the treatment period. The dose of Atenolol was determined according to its pharmacokinetic parameters. Clinically effective plasma concentration as a hypotensive drug was obtained after the injection of 0.1 mg/155+/-15 gm of body weight of the drug. The Catharanthus roseus leaves extract made significant changes in each cardiovascular parameter after investigation. Catharanthus roseus leaves extract treated animals have shown the hypotensive effects. Hypotensive effects were also shown by Atenolol.
Cecropia pachystachya Mart. is popularly called “ambay” and extensively used in herbal medicine of South America for cough and asthma. In Argentina it grows in neotropical rainforest (Ntr C.p.) and in a temperate region (Tp C.p.). In a previous work we showed their hypotensive properties with different potency and toxicity, and now we studied the Tp C.p. effects in isolated heart from rats and central effects of both plants on the open-field test for mice. Tp C.p. produced a positive inotropic effect on isolated rat hearts, which was not affected by 1 microM propranolol, suggesting that it is not due to a beta-adrenergic effect. In contrast, it was prevented by pretreatment with high [K](o) media, which stimulates the Na,K-ATPase pump, suggesting an inhibition of the pump by “ambay”, as digital do. In the open-field test, both Ntr C.p. and Tp C.p. similarly decreased the spontaneous locomotion and exploratory behavior of mice at doses between 180 and 600 mg/kg. Ntr C.p. potentiated the effect of 3 mg/kg diazepam to one similar to 10 mg/kg diazepam, but was not antagonized by 0.5 mg/kg flumazenil. Amphetamine at 5 mg/kg prevented the sedative effect of Ntr C.p. Chromatographic analysis showed that both plants have a qualitatively similar fingerprint but quantitatively differed in at least three components. Although the purpose was not to identify them, both plants have at least 10 compounds. Two of them were in higher amount in Tp C.p. than in Ntr C.p., and then, they could be responsible for the cardiovascular toxicity of Tp C.p. In conclusion, the results suggest that ambay has cardiotonic and sedative properties. The sedative effect could be useful in cough treatment. The extract resulted additive to benzodiazepines but it did not bind to the same site on GABA-A receptor, and it was interfered by the dopamine release produced with amphetamine.
Cirsium japonicum De Candole is widely used in traditional herbal medicine for the treatment of hemorrhage, hypertension or blood circulation in Korea. In this work, we investigated the vasorelaxant activity of an aqueous extract of C. japonicum whole plant (CjEx) and its possible mechanism in isolated rat thoracic aortic rings constricted with norepinephrine (NE; 300 nmol/l). CjEx elicited an acute relaxation in endothelium-intact rings in a concentration-dependent manner (0.1-1.0 mg/ml). This relaxation was eliminated by the removal of the endothelium and pretreatment with N(G)-nitro-L-arginine (10 micromol/l), methylene blue (1 micromol/l) or diphenylhydramine (10 micromol/l), but indomethacin (10 micromol/l) atropine (100 nmol/l), [D-Pro(2), D-Trp(7,9)] substance P (5 micromol/l) or HOE-140 (10 nmol/l) did not affect the relaxation. The results indicate that the response to CjEx involves enhancement of the nitric oxide-cyclic guanosine monophosphate system, and that it occurs via histamine H(1)-receptor. Our findings may contribute to better understanding of the potential link between the clinical use and its beneficial effects on vascular health.
Ethnopharmacological relevance: Citrus limetta Risso (Rutaceae) is widely used in Mexico for healing purposes, among them as antihypertensive treatment.
Aim of the study: To assess the antihypertensive effect of C. limetta leaves as one of its ethnomedical uses.
Materials and methods: The acute response of blood pressure to angiotensin II administration was measured in mice. Additionally, the acute oral toxicity profiles were determined.
Results: The findings of the current investigation showed that different concentrations of the aqueous extract prevented the raise of systolic blood pressure (p< or =0.001 vs. vehicle), diastolic blood pressure (p< or =0.0002 vs. vehicle) and mean blood pressure (p< or =0.0000 vs. vehicle); with a dose dependent effect for diastolic pressures at 125-500mg/kg dosages. The 500 and 1000mg/kg doses inhibited the action of Ang II in similar extent to telmisartan. Toxic signs or deaths were not observed in mice treated at 2000mg/kg of C. limetta extract.
Conclusions: All doses of C. limetta aqueous extract, used in this assay, were safe and effective.
The stems of Clerodendron trichotomum have been traditionally used for treatment of hypertension in far East Asia including China, Korea, and Japan. Bioassay-guided fractionation and purification of the EtOAc-soluble extract of Clerodendron trichotomum afforded acteoside (1), leucosceptoside A (2), martynoside (3), acteoside isomer (4), and isomartynoside (5). The angiotensin converting enzyme (ACE) activities were significantly inhibited by the addition of these phenylpropanoid glycosides (1-5) in a dose-dependent manner of which IC(50) values were 373+/-9.3 microg/ml, 423+/-18.8 microg/ml, 524+/-28.1 microg/ml, 376+/-15.6 microg/ml, 505+/-26.7 microg/ml, respectively. These results suggest that the antihypertensive effect of Clerodendron trichotomum may be, at least in part, due to ACE inhibitory effect of phenylpropanoid glycosides.
Ethnopharmacological relevance: The fruits of Cocos nucifera Linn. (Arecaceae) have long been used in traditional medicine for the treatment of cardio-metabolic disorders.
Aim of the study: To evaluate the ethanolic extract of Cocos nucifera Linn. endocarp (CNE) for its vasorelaxant activity on isolated rat aortic rings and antihypertensive effects in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats.
Materials and methods: Cocos nucifera Linn. endocarp was extracted with ethanol and characterized by HPLC. CNE was examined for its in vitro vascular relaxant effects in isolated norepinephrine, phenylephrine or potassium chloride pre-contracted aortic rings (both intact endothelium and denuded). In vivo anti-hypertensive studies were conducted in DOCA salt-induced uninephrectomized male Wistar rats.
Results: Removal of endothelium or pretreatment of aortic rings (intact endothelium) with l-NNA (10μM) or ODQ (10 μM) followed by addition of contractile agonists prior to CNE significantly blocked the CNE-induced relaxation. Indomethacin (10μM) and atropine (1 μM) partially blocked the relaxation, whereas glibenclamide (10 μM) did not alter it. CNE significantly reduced the mean systolic blood pressure in DOCA salt-induced hypertensive rats (from 185.3 ± 4.7 mmHg to 145.6±6.1 mmHg). The activities observed were supported by the polyphenols, viz. chlorogenic acid, vanillic acid and ferulic acid identified in the extract.
Conclusions: These findings reveal that the vasorelaxant and antihypertensive effects of CNE, through nitric oxide production in a concentration and endothelium-dependent manner, is due to direct activation of nitric oxide/guanylate cyclase pathway, stimulation of muscarinic receptors and/or via cyclooxygenase pathway.
Crataegus pinnatifida Bunge
Hawthorn leaves, flowers and fruits are used to treat mild hypertension alone or in conjunction with prescribed drugs. In a pilot study of mild hypertension, there were promising hypotensive responses to 500 mg of hawthorn per day after 10 weeks. Walker et al.  investigated the effects of hawthorn for hypertension in patients with type II diabetes. Results showed there was a significant group difference in mean diastolic blood pressure reductions (P = 0.035): the hawthorn group showed greater reductions (baseline: 85.6 mmHg, 95% confidence interval [CI] = 83.3 to 87.8; outcome: 83.0 mmHg, 95% CI = 80.5 to 85.7) than the placebo group (baseline: 84.5 mmHg, 95% CI = 82 to 87; outcome: 85.0 mmHg, 95% CI = 82.2 to 87.8). There was no group difference in systolic blood pressure reduction from baseline (3.6 and 0.8 mmHg for hawthorn and placebo groups, respectively; P = 0.329). In a double-blind, placebo-controlled clinical trial to determine the effects of the C. curvisepala leaves and flowers for mild hypertension, results showed a significant decrease in both systolic and diastolic blood pressure after 3 months (p < 0.05), and a time-dependent antihypertensive effect .
The mechanism for hypotension of Hawthorn is regard to be related to the inhibition of Angiotensin I – Converting Enzyme (ACE), which is considered to be a useful therapeutic approach in the treatment of high blood pressure. Within the enzyme cascade of the renin–angiotensin system, ACE removes histidyl-leucine from angiotensin I to form the octapeptide angiotensin II, which is one of the most potent vasoconstrictors. Angiotensin II also stimulates the synthesis and release of aldosterone which promotes sodium and water retention, resulting in increasing of blood pressure. Using an in vitro ACE-inhibition assay, Inokuchi et al.  found ACE-inhibitory fractions in Hawthorn fruits. Lacaille-Dubois et al. found flavonoids and proanthocyanidins from the flowers and leaves of C. oxyacantha/ monogyna demonstrated inhibitory activity at 0.33 mg/ml, while phenolic acids showed no significant ACE-inhibition.
Aim of the study: Coriander (Coriandrum sativum) is traditionally used for various gastrointestinal and cardiovascular disorders and this study was designed to rationalize its use in dyspepsia, abdominal colic, diarrhea, hypertension and as diuretic.
Materials and methods: Coriander crude extract (Cs.Cr) was evaluated through in vitro and in vivo techniques.
Results: Cs.Cr caused atropine sensitive stimulatory effect in isolated guinea-pig ileum (0.1-10 mg/ml). In rabbit jejunum preparations, Cs.Cr evoked a similar contractile response but in the presence of atropine, it exhibited relaxation against both spontaneous and high K(+) (80 mM)-induced contractions as well as shifted the Ca(2+) concentration-response curves to right, similar to that caused by verapamil. Cs.Cr (1-30 mg/ml) caused fall in arterial blood pressure of anesthetized animals, partially blocked by atropine. Cs.Cr produced vasodilatation against phenylephrine and K(+) (80 mM)-induced contractions in rabbit aorta and cardio-depressant effect in guinea-pig atria. Cs.Cr produced diuresis in rats at 1-10mg/kg. Bio-assay-directed fractionation revealed the separation of spasmogenic and spasmolytic components in the aqueous and organic fractions respectively.
Conclusions: These results indicate that coriander fruit exhibits gut stimulatory, inhibitory and hypotensive effects mediating possibly through cholinergic, Ca(2+) antagonist and the combination of these mechanisms respectively. diuretic activity adds value to its use in hypertension.
The water extract from Coscinium fenestratum (Gaertn.) Colebr. (CF extract) was tested for hypotensive and vasorelaxant effects. Acute and subchronic toxicity as well as motor activity of CF extract were also evaluated. The present study demonstrates that CF extract is effective in reducing blood pressure in anesthetized normotensive rats. This effect is shown to be dose-related and rapid in onset. The extract showed an endothelium-dependent and independent vasorelaxant activity in isolated aortic rings precontracted with phenylephrine (1 microM) and KCl (60 mM). The capacity of L-NAME (100 microM), an inhibitor of nitric oxide synthase, to reduce the vasorelaxant action of the extract indicates the involvement of nitric oxide. In the acute toxicity test, an oral dose of 5000 mg/kg of the CF extract did not produce mortality or significant changes of the general behavior of animals and gross appearance of internal organs of rats. Similarly, in the subchronic toxicity test, an oral dose of 2500 mg/kg/day of the CF extract given to rats for 90 days did not cause any significant change of any of the parameters observed when compared with those of the control animals. Moreover, the CF extract did not produce any effect on the central nervous system when spontaneous motor activity in rats was assessed. However, because some average hematological and blood chemistry values were found to be statistically different, further studies, including chronic toxicity test, should be done to confirm the safety of this plant when it is used over a long period of time.
In this study, the effects of saffron (Crocus sativus) stigma aqueous extract and two active constituents, crocin and safranal, were investigated on blood pressure of normotensive and desoxycorticosterone acetate-induced hypertensive rats. Three doses of crocin (50, 100 and 200 mg/kg), safranal (0.25, 0.5 and 1 mg/kg) and the aqueous extract (2.5, 5 and 10 mg/kg) were administered intravenously in different groups of normotensive and hypertensive animals and their effects on mean arterial blood pressure (MABP) and heart rate (HR) were evaluated. The aqueous extract of saffron stigma, safranal and crocin reduced the MABP in normotensive and hypertensive anaesthetized rats in a dose-dependent manner. For example, administrations of 10 mg/kg of aqueous extract, 1 mg/kg of safranal and 200 mg/kg of crocin caused 60 +/- 8.7, 50 +/- 5.2 and 51 +/- 3.8 mmHg reductions in MABP, respectively. It can be concluded that the aqueous extract of saffron stigma has hypotensive properties which appear to be attributable, in part, to the actions of two major constitutes of this plant, crocin and safranal. It seems that safranal is more important than crocin for lowering down blood pressure of rats.
A pharmacological inhibition of nitric oxide synthase (NOS) in rats for 4-6 weeks produces renal vasoconstriction, renal dysfunction, and severe hypertension. The present study was aimed at investigating whether Cudrania tricuspidata (C. tricuspidata) water extract ameliorates N(G)-Nitro-L-arginine methylester (L-NAME)-induced hypertension. Treatment of L-NAME (60 mg/L drinking water, 4 weeks) causes a sustained increase in systolic blood pressure (SBP). The concentration of plasma NO metabolites and NO/cGMP productions in the vascular tissues of the L-NAME-treated group were significantly reduced as compared with those in the control. C. tricuspidata water extract blocked increase of SBP in the L-NAME-treated group and restored SBP to normal level. Futhermore, C. tricuspidata water extract was able to preserve the vascular NO/cGMP production and plasma NO metabolites concentration. However, there are no changes in the expression of ecNOS and iNOS of thoracic aorta among the rats of control, L-NAME-treated group, and L-NAME and C. tricuspidata water extract co-treated group. The urinary sodium level, urine volume, and creatinine clearance were significantly higher in rats co-treated with C. tricuspidata water extract and L-NAME than in L-NAME-treated group. Taken together, these results suggest that C tricuspidata water extract prevents the increase of SBP in the L-NAME-induced hypertension that may have been caused by enhanced generation of vascular NO/cGMP.
Bioassay-guided fractionation of the EtOAc-soluble extract of Cuscuta japonica afforded 3,5-Di-O-caffeoylquinic acid (1). methyl 3,5-Di-O-caffeoylquinate (2). 3,4-Di-O-caffeoylquinic acid (3). and methyl 3,4-Di-O-caffeoylquinate (4). Purification of these compounds was conducted with the application of various chromatographic methods. The structures of the compounds were elucidated on the basis of MS and NMR data analysis. Compounds 1-4 inhibited the angiotensin I converting enzyme activity in a dose-dependent manner. Compounds 1-4 showed the 50% inhibitory concentration values of 596, 483, 534, and 460 micro M, respectively. The presence of these active components may be responsible, at least in part, for the antihypertensive action of traditional crude drug Cuscuta Semen.