Jiaogulan Research

In this section you will find a selection of published jiaogulan research articles as listed on PubMed. A serviceof the U.S. National Library of Medicine, PubMed includes over 19 million citations from MEDLINE and other life science journals for biomedical articles back to 1948.

Phytopreventative effects of Gynostemma pentaphyllum against acute Indomethacin-induced gastrointestinal and renal toxicity in rats.

Author: Hesse C, Razmovski-Naumovski V, Duke CC, Davies NM, Roufogalis BD.
Source: Phytother Res. 2007 Jun;21(6):523-30.

In the present study, the phytoprotective effects of gypenosides from Gynostemma pentaphyllum throughout the gastrointestinal tract and kidney were examined in indomethacin-treated rats. Indomethacin induced gastric and intestinal damage as well as renal toxicity after a single toxicological dose (10 mg/kg) in rats. Acute oral administration of the gypenoside extract (200 mg/kg) significantly reduced gastric and intestinal toxicity induced by indomethacin as measured by ulceration, caecal haemoglobin and plasma haptoglobin. A significant decrease in small intestinal lactose fermenting enterobacteria was evident in animals treated with indomethacin and those pre-treated with G. pentaphyllum then indomethacin. In the renal system, kidney toxicity was evident after indomethacin and in animals pre-treated with indomethacin plus G. pentaphyllum with an increase in urinary N-acetyl-beta-glucosaminidase and a decrease in urinary sodium and chloride electrolyte output. However, a significant increase in urinary microprotein in indomethacin-treated animals was not present in indomethacin plus G. pentaphyllum-treated animals. These studies demonstrate the efficacy of Gynostemma pentaphyllum in lowering gastrointestinal damage induced by indomethacin. The results suggest further investigations of Gynostemma gypenosides are warranted to examine the mechanisms of this phytoprotective activity. (c) 2007 John Wiley & Sons, Ltd.


The anti-gastric ulcer effect of Gynostemma pentaphyllum Makino.

Author: Rujjanawate C, Kanjanapothi D, Amornlerdpison D.
Source: Phytomedicine. 2004 Jul;11(5):431-5.

Gynostemma pentaphyllum is an oriental medicinal herb reputed to have broad-spectrum activities. The plant's principal saponin components are structurally similar to those found in ginseng plants and this similarity is assumed to be responsible for the claimed activities. The present study was undertaken to evaluate a G. pentaphyllum butanol fraction (GPB) for its anti-gastric ulcer activity using experimental models. Oral administration of the GPB at 200 and 400 mg/kg body wt. significantly inhibited gastric ulcer formation induced by indomethacin, HCl/EtOH and water-immersion restraint stress in rats. In pylorus-ligated rats, pretreatment with the GPB had no effect on gastric volume, pH or acidity output, thus indicating a lack of anti-secretory effect. In ethanol-induced ulcerated rats, gastric wall mucus and hexosamine content were markedly preserved by GPB pretreatment. The findings indicate that the butanol fraction of G. pentaphyllum possesses gastroprotective potential related to the preservation of gastric mucus synthesis and secretion.

Protective effect of gypenosides against oxidative stress in phagocytes, vascular endothelial cells and liver microsomes.

Author: Li L, Jiao L, Lau BH.
Source: Cancer Biother. 1993 Fall;8(3):263-72.

The action of gypenosides (GP, saponins of Gynostemma pentaphyllum, a Chinese medicinal herb) as an antioxidant was studied using various models of oxidant stress in phagocytes, liver microsomes and vascular endothelial cells. The results show that GP decreased superoxide anion and hydrogen peroxide content in human neutrophils and diminished chemiluminescent oxidative burst triggered by zymosan in human monocytes and murine macrophages. An increase of lipid peroxidation induced by Fe2+/cysteine, ascorbate/NADPH or hydrogen peroxide in liver microsomes and vascular endothelial cells was inhibited by GP. It was also found that GP protected biomembranes from oxidative injury by reversing the decreased membrane fluidity of liver microsomes and mitochondria, increasing mitochondrial enzyme activity in vascular endothelial cells and decreasing intracellular lactate dehydrogenase leakage from these cells. The extensive antioxidant effect of GP may be valuable to the prevention and treatment of various diseases such as atherosclerosis, liver disease and inflammation.

[Scavenging effects of Astragalus and Gynostemma pentaphyllum with its product on O2- and OH]

Author: Ma Z, Yang Z.
Source: Zhong Yao Cai. 1999 Jun;22(6):303-6. Chinese.

The scavenging effects of Astragalus and Gynostemma pentaphyllum with its products on O2-. (produced by the autoxidation of pyrogallol) and .OH (generated from the Fenton reaction) were investigated by electrochemical method. The results showed that they could scavenge the active oxygen free radicals effectively, however, their scavenge ability was different for O2-. and .OH. The inhibitory effect of Ginsenoside Rb1 and Astragaloside IV on O2-. and .OH was the most strongest. Their IC50 values were calculated respectively. The scavenging ability of Astragalus samples on O2-. was in the order of the following: astragaloside IV > crude radix astragali > mongolia radix astragali > hebei radix astragali > radix astragali > radix astragali mixfry with honey; and the scavenging effect on .OH was: astragaloside IV > hebei radix astragali > radix astragali mix-fry with honey > radix astragali > crude radix astragali > mongolia radix astragali. The scavenging activity of gynostemma samples on O2-. was: ginsenoside Rb1 > gynostemma jujube tea > tabellae Jiaogulanosidi > anguo market gynostemma > hebei qingxian gynostemma; while on .OH, the inhibitory ability was: ginsenoside Rb1 > gynostemma jujube tea > anguo market gynostemma > hebei qingxian gynostemma > tabellae Jiaogulanosidi.

Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and gypenosides III and VIII in anaesthetized guinea-pigs.

Author: Circosta C, De Pasquale R, Palumbo DR, Occhiuto F.
Source: J Pharm Pharmacol. 2005 Aug;57(8):1053-8.

The bronchodilatory activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in anaesthetized guinea-pigs and compared with two of its isolated gypenosides (III and VIII). The results showed that the intravenous administration of the decoction of G. pentaphyllum (2.5, 5 or 10 mg kg(-1)) decreased bronchial resistance in basal conditions and significantly (P < 0.01) reduced (68% inhibition) the bronchoconstrictor action of histamine. Furthermore, the extract antagonized (80% inhibition) the bronchoconstrictor response induced by the antigen in sensitized guinea-pigs. Gypenosides III (0.7 mg kg(-1), i.v.) and VIII (0.3 mg kg(-1), i.v.) caused a similar protective effect in both experimental models used; however, the duration and the intensity of the action was less than that of the extract containing corresponding quantities of gypenosides III and VIII. This study confirmed the validity of the traditional use of this plant in the treatment of asthma and other respiratory disorders.

Gynostemma pentaphyllum decreases allergic reactions in a murine asthmatic model.

Author: Huang WC, Kuo ML, Li ML, Yang RC, Liou CJ, Shen JJ.
Source: Am J Chin Med. 2008;36(3):579-92.

The increasing incidence of asthma in developing countries emphasizes the importance of identifying more effective treatments that have low cost. Gynostemma pentaphyllum (Thunb.) Makino (Cucurbitaceae), a common herbal tea in China, has been used to treat lung inflammation. Since the Th2 cytokines are the major mediators in the pathogenesis of asthma, Th1-biased immune responses caused by G. pentaphyllum might have the potential to relieve asthmatic symptoms. We hypothesized that oral administration of G. pentaphyllum extracts might suppress Th2 cytokine-induced airway inflammation responses in ovalbumin (OVA)-sensitive mice. BALB/c mice were sensitized with intraperitoneal injection and challenged 3 times with OVA inhalation (IH) (the IH3 model). G. pentaphyllum was orally administered for 7 consecutive days before the end of the OVA challenge. In the IH5 model, 2 more OVA challenges were administered to mimic the encounter with an allergen after drug treatment. G. pentaphyllum extracts significantly attenuated airway hyperresponsiveness (AHR) and inhibited eosinophil infiltration in mice in both models. Serum OVA-specific antibodies were also reduced with the treatment. Decreased Th2-type cytokines and increased IFN-gamma were detected in the cultures of OVA-activated splenocytes from treated mice. Our results suggest that G. pentaphyllum extracts might be beneficial for asthma airway inflammation through the suppression of Th2 activity.

A novel LXR-alpha activator identified from the natural product Gynostemma pentaphyllum.

Author: Huang TH, Razmovski-Naumovski V, Salam NK, Duke RK, Tran VH, Duke CC, Roufogalis BD.
Source: Biochem Pharmacol. 2005 Nov 1;70(9):1298-308.

Liver X receptors (LXR) play an important role in cholesterol homeostasis by serving as regulatory sensors of cholesterol levels in tissues. The present study reports a novel LXR-alpha activator, (20S)-2alpha, 3beta, 12beta, 24(S)-pentahydroxydammar-25-ene 20-O-beta-d-glucopyranoside (TR1), a dammarane-type gynosaponin, isolated from the herbal medicine, Gynostemma pentaphyllum. Gynosaponin TR1 demonstrated greater selectivity toward activation of the LXR-alpha isoform than LXR-beta in HEK293 cells. TR1 selectively enhanced LXR-mediated transcriptional activation and protein expression of ABCA1 and apoE gene expression and secretion in THP-1-derived macrophages. The selectivity of TR1 for LXR-alpha was consistent with ligand docking studies, which showed favourable interaction of TR1 in the LXR-alpha-binding domain, whereas the presence of the sugar substituent interfered with binding to the LXR-beta site. Findings from the present study may provide insight into the development of pharmaceutical agents for treating atherosclerosis.

[Influence of gypenoside on serum lipoprotein and atherosclerosis in hyperlipidaemia animals]

Author: Qi G, Zhang L, Li C.
Source: Zhongguo Zhong Yao Za Zhi. 1996 Sep;21(9):562-4 inside back cover. Chinese.

The result of the study indicates that gypenoside (GP, i.g.) can suppress the rise of serum cholesterol (CHO) and triglyceride (TRIG) in hyperlipidaemia mice and lower the content of CHO, TRIG and LDL in hyperlipidaemia quails. The study also shows that GP has a protective effect on diffuse lipoidosis in liver and atherosclerosis in hyperlipidaemia quails, and that GP can lower the lipoprotein levels in hyperlipidaemia animals.

Anti-hyperlipidemic and hypoglycemic effects of Gynostemma pentaphyllum in the Zucker fatty rat.

Author: Megalli S, Davies NM, Roufogalis BD.
Source: J Pharm Pharm Sci. 2006;9(3):281-91.

Gynostemma pentaphyllum is a traditional Chinese medicine used for a variety of conditions, including elevated cholesterol. We have examined the pharmacological anti-hyperlipidemic and hypoglycemic effectiveness of Gynostemma pentaphyllum in the obese Zucker fatty diabetic rat model. After treatment for 4 days Gynostemma pentaphyllum 250 mg/kg reduced triglyceride (33%), total cholesterol, (13%) and low density lipoprotein cholesterol levels (33%). These effects were dose-dependent and maintained for at least 5 weeks. Chronic treatment for 3-5 weeks also reduced post-prandial hypertriglyceridemia induced by olive oil 10 mg/kg in the Zucker fatty rats but had no significant effect in lowering sucrose-induced hyperglycemia in Sprague-Dawley rats. A novel regulation by Gynostemma of glucose levels was also observed in the Zucker fatty rat model. In a glucose tolerance test in obese and lean Zucker rats pretreatment with Gynostemma pentaphyllum 250 mg/kg demonstrated glucose levels were significantly less 2 hours post challenge (20%) in the Gynostemma pentaphyllum obese rats compared to the control group. Gynostemma pentaphyllum did not significantly reduce glucose levels at 120 min in the lean strain, in contrast to the 20% decrease seen in the obese rat. In vitro, Gynostemma pentaphyllum inhibited alpha-glucosidase activity (50% inhibition at 42.8), which compared to acarbose (50% at 53.9 microg/mL). The improvement in glucose tolerance at 120 min by Gynostemma pentaphyllum in obese Zucker fatty rats but not lean rats suggests that it may improve insulin receptor sensitivity and together with the significant reduction of hypertriglyceridemia, cholesterol and low density lipoprotein cholesterol suggests that Gynostemma should be examined further by oral hypoglycemic/anti-hyperlipidemic therapy.

Phytopreventative anti-hyperlipidemic effects of Gynostemma pentaphyllum in rats.

Author: Megalli S, Aktan F, Davies NM, Roufogalis BD.
Source: J Pharm Pharm Sci. 2005 Sep 16;8(3):507-15.

PURPOSE: Gynostemma pentaphyllum is widely used in traditional Chinese medicine. Preliminary studies indicate Gynostemma isolated triterpine glycosides lower cholesterol. Our studies examine anti-hyperlipidemic effects of gypenosides. METHODS: Gynostemma activity was examined in poloxamer P407 induced hyperlipidemia in rats. RESULTS: 1 g/kg P407 induced plasma triglyceride (25 fold), total cholesterol (6 fold), low density lipoprotein cholesterol (LDL) (7 fold), high density lipoprotein cholesterol (HDL) (1.6 fold), and nitrite (8 fold). After acute (4 days) and chronic (12 days) oral administration the gypenoside extract (250 mg/kg) reduced triglyceride (53% and 85%, respectively) and total cholesterol levels (10% and 44%, respectively). No significant effects on LDL or HDL cholesterol were observed. The gypenosides reduced nitrite approximately 80%. Similar results were obtained with atorvastatin (75 mg/kg for 4 days); except that LDL cholesterol was reduced (17%) and HDL cholesterol increased. 50% of lipoprotein lipase (LPL) plasma activity was inhibited by approximately 20 microM P407. Gynostemma had no effect on LL, however, it reversed the P407 inhibition of LPL activity in a concentration-dependent manner, with a 2-fold increase at approximately 10 microg/ml. CONCLUSIONS: These studies demonstrate efficacy of Gynostemma pentaphyllum in lowering triglyceride, cholesterol and nitrite in acute hyperlipidemia. The results suggest further investigations of Gynostemma gypenosides are warranted to examine the mechanisms of this activity.

Traditional Chinese medicine in treatment of hyperlipidaemia.

Author: La Cour B, M�lgaard P, Yi Z.
Source: J Ethnopharmacol. 1995 May;46(2):125-9.

In the search of new products for treatment of hyperlipidaemia with a low frequency of side effects a decoction of Crataegus cuneata, Nelumbo nucifera and Gynostemma pentaphylla has been tested. A reduction of triglyceride and cholesterol was seen.

Gypenoside XLIX, a naturally occurring PPAR-alpha activator, inhibits cytokine-induced vascular cell adhesion molecule-1 expression and activity in human endothelial cells.

Author: Huang TH, Tran VH, Roufogalis BD, Li Y.
Source: Eur J Pharmacol. 2007 Jun 22;565(1-3):158-65. Epub 2007 Mar 24.

Vascular cell adhesion molecule-1 (VCAM-1) is involved in several diseases, including chronic inflammation and atherosclerosis. Inhibition of the expression of this adhesion molecule is one of the key targets of anti-inflammatory, anti-cancer and anti-atherosclerotic drugs. Gynostemma pentaphyllum is a traditional medicine widely used in the treatment of respiratory inflammation, hyperlipidemia and atherosclerosis. However, its molecular mechanisms of action are still largely unknown. Gypenoside XLIX, a dammarane-type glycoside, is a prominent component of G. pentaphyllum. We have recently demonstrated Gypenoside XLIX to be a selective peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gypenoside XLIX concentration-dependently (0-300 microM) inhibited VCAM-1 promoter activity after induction by cytokine tumor necrosis factor (TNF)-alpha in human umbilical vein endothelial cells (HUVECs) transfected with promoter-reporter construct pVCAM-1-LUC. Furthermore, Gypenoside XLIX inhibited TNF-alpha-induced VCAM-1 mRNA and protein overexpression in HUVECs. The result of the enzyme immunoassay demonstrated that Gypenoside XLIX inhibited TNF-alpha-induced increase in cell surface VCAM-1 protein levels in HUVECs. In the present study we show that activities of Gypenoside XLIX are similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, Gypenoside XLIX-induced inhibition on TNF-alpha-stimulated VCAM-1 promoter hyperactivity was completely abolished by a selective blocker of PPAR-alpha, MK-886. Thus, our findings suggest that Gypenoside XLIX inhibits cytokine-induced VCAM-1 overexpression and hyperactivity in human endothelial cells via a PPAR-alpha-dependent pathway. These data provide new insight into the rational basis of the use of the traditional Chinese herbal medicine G. pentaphyllum in the treatment of inflammatory and cardiovascular diseases, including atherosclerosis.

Gypenoside XLIX, a naturally occurring gynosaponin, PPAR-alpha dependently inhibits LPS-induced tissue factor expression and activity in human THP-1 monocytic cells.

Author: Huang TH, Tran VH, Roufogalis BD, Li Y.
Source: Toxicol Appl Pharmacol. 2007 Jan 1;218(1):30-6. Epub 2006 Oct 25.

Tissue factor (TF) is involved not only in the progression of atherosclerosis and other cardiovascular diseases, but is also associated with tumor growth, metastasis, and angiogenesis and hence may be an attractive target for directed cancer therapeutics. Gynostemma pentaphyllum (GP) is widely used in the treatment of various cardiovascular diseases including atherosclerosis, as well as cancers. Gypenoside (Gyp) XLIX, a dammarane-type glycoside, is one of the prominent components in GP. We have recently reported Gyp XLIX to be a potent peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gyp XLIX (0-300 microM) concentration dependently inhibited TF promoter activity after induction by the inflammatory stimulus lipopolysaccharide (LPS) in human monocytic THP-1 cells transfected with promoter reporter constructs pTF-LUC. Furthermore, Gyp XLIX inhibited LPS-induced TF mRNA and protein overexpression in THP-1 monocyte cells. Its inhibition of LPS-induced TF hyperactivity was further confirmed by chromogenic enzyme activity assay. The activities of Gyp XLIX reported in this study were similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, the Gyp XLIX-induced inhibitory effect on TF luciferase activity was completely abolished in the presence of the PPAR-alpha selective antagonist MK-886. The present findings suggest that Gyp XLIX inhibits LPS-induced TF overexpression and enhancement of its activity in human THP-1 monocytic cells via PPAR-alpha-dependent pathways. The data provide new insights into the basis of the use of the traditional Chinese herbal medicine G. pentaphyllum for the treatment of cardiovascular and inflammatory diseases, as well as cancers.

Protection of hippocampal slices against hypoxia/hypoglycemia injury by a Gynostemma pentaphyllum extract.

Author: Schild L, Roth A, Keilhoff G, Gardemann A, Br�demann R.
Source: Phytomedicine. 2009 Aug;16(8):734-43. Epub 2009 Apr 29.

In transverse hippcampus slices a short period of hypoxia/hypoglycemia induced by perfusion with O(2)/glucose-free medium caused early loss and incomplete restoration of evoked field potentials to only 50% in the CA(1) region. We report about a study investigating the effect of an ethanolic Gynostemma pentaphyllum extract in this system. When given with reperfusion the extract completely protected the cells of the slices from functional injury. The extract also protected at the subcellular level isolated mitochondria which had been subjected to hypoxia/reoxygenation in combination with elevated extramitochondrial Ca(2+) concentration from functional injury. In isolated mitochondria the extract protected from Ca(2+)-induced opening of the mitochondrial permeability transition pore and reduced lipid peroxidation. Our data demonstrate that the ethanolic extract of Gynostemma pentaphyllum has a high potential to protect from ischemia/reperfusion injury. It should be beneficial as prophylactic nutrition supplement and during revascularization of arterial blood vessels from stroke and other ischemic events such as coronary occlusion.
Gypenosides protect primary cultures of rat cortical cells against oxidative neurotoxicity.

Author: Shang L, Liu J, Zhu Q, Zhao L, Feng Y, Wang X, Cao W, Xin H.
Source: Brain Res. 2006 Aug 2;1102(1):163-74. Epub 2006 Jun 27.

Gypenosides (GPs) were tested for their ability to protect primary cultures of immature cortical cells against oxidative glutamate toxicity. In immature neural cells, glutamate cytotoxicity is known to be mediated by the inhibition of cystine uptake, leading to depletion of intracellular glutathione (GSH). The depletion of GSH impairs cellular antioxidant defenses resulting in oxidative stress and cell death. We found that pretreatment with GPs (100-400 microg/ml) significantly protected cells from glutamate-induced cell death. It was therefore of interest to investigate whether GPs protect cortical cells against glutamate-induced oxidative injury through preventing GSH depletion. Results show that GPs significantly up-regulated mRNAs encoding gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione reductase (GR) and enhanced their activities for GSH synthesis as well as recycle. Furthermore, GPs lowered the consumption of GSH through decreased accumulation of intracellular peroxides, leading to an increase in the intracellular GSH content. GPs were also found to prevent lipid peroxidation and reduce the influx of Ca(2+) which routinely follows glutamate oxidative challenge. GPs treatment significantly blocked glutamate-induced decrease in levels of Bcl-2 and increase in Bax, leading to a decrease in glutamate-induced apoptosis. Thus, we conclude that GPs protect cortical cells by multiple antioxidative actions via enhancing intracellular GSH, suppressing glutamate-induced cytosolic Ca(2+) elevation and blocking glutamate-induced apoptosis. The novel role of GPs implies their remarkable preventative and therapeutic potential in treatment of neurological diseases involving glutamate and oxidative stress.
Protective effect of gypenosides on DNA and RNA of rat neurons in cerebral ischemia-reperfusion injury.

Author: Qi G, Zhang L, Xie WL, Chen XY, Li JS.
Source: Acta Pharmacol Sin. 2000 Dec;21(12):1193-6.

AIM: To observe the protective effect of gypenosides (GP) on the neurons of hippocampus, cerebral cortex, corpus striatum, and dentate gyrus in cerebral ischemia-reperfusion injury of rats. METHODS: Modified 4-vessel occlusion (4-VO) method was used to establish the model of acute global ischemia. The acridine orange (AO) staining method was used to observe the DNA and RNA contents of cerebral ischemia-reperfusion injury model in the areas. RESULTS: The fluorescent intensity (reflecting DNA and RNA contents) of the DNA and RNA in the areas of cerebral ischemia-reperfusion injury was markedly abated compared with the normal control group. In the group of ig GP (100 mg/kg) it was enhanced compared with the model group and was the same as the normal control group. CONCLUSION: The injury of the DNA and RNA in the areas of ischemia-reperfusion model was decreased by GP.
Analysis of the inhibitory effect of gypenoside on Na(+), K (+)-ATPase in rats' heart and brain and its kinetics.

Author: Han XY, Wei HB, Zhang FC.
Source: Chin J Integr Med. 2007 Jun;13(2):128-31.

OBJECTIVE: To study the effects of gypenoside (Gyp) on the activity of microsomal Na(+), K(+)-ATPase in rat's heart and brain in vitro. METHODS: The microsomal Na(+), K(+)-ATPase was prepared from rat's heart and brain by differential centrifugation. The activity of microsomal Na(+), K(+)-ATPase was assayed by colorimetric technique. Enzyme kinetic analysis method was used to analyze the effect of Gyp on the microsomal Na(+), K(+)-ATPase of rats. RESULTS: Gyp reversibly inhibited the brain and heart's microsomal Na(+), K(+)-ATPase in a concentration-dependent manner, and showed a more potent effect on enzyme in the brain. The IC(50) of Gyp for the heart and brain were 58.79+/-8.05 mg/L and 52.07+/-6.25 mg/L, respectively. The inhibition was enhanced by lowering the Na(+), or K(+) concentrations or increasing the ATP concentration. Enzyme kinetic studies indicated that the inhibitory effect of Gyp on the enzyme is like that of competitive antagonist of Na(+), the counter-competitive inhibitor for the substrate ATP, and the mixed-type inhibitor for K(+). CONCLUSION: Gyp displays its cardiotonic and central inhibitory effects by way of inhibiting heart and brain's microsomal Na(+), K(+)-ATPase activities in rats.
The possible mechanisms by which phanoside stimulates insulin secretion from rat islets.

Author: Hoa NK, Norberg A, Sillard R, Van Phan D, Thuan ND, Dzung DT, J�rnvall H, Ostenson CG.
Source: J Endocrinol. 2007 Feb;192(2):389-94.

We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3 x 3 and 16 x 7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 microM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3 x 3 mM glucose with 150 muM phanoside and 0 x 25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 microM phanoside alone. At 16 x 7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0 x 25 mM diazoxide (P<0 x 01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3 x 3 mM glucose but did not further increase the release at 16 x 7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3 x 3 mM glucose but decreased at 16 x 7 mM glucose (P<0 x 01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 microM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.
Potential hypoglycemic effect of an ethanol extract of Gynostemma pentaphyllum in C57BL/KsJ-db/db mice.

Author: Yeo J, Kang YJ, Jeon SM, Jung UJ, Lee MK, Song H, Choi MS.
Source: J Med Food. 2008 Dec;11(4):709-16.

This study was conducted to evaluate the antihyperglycemic effect of an extract of Gynostemma pentaphyllum Makino, containing standardized concentrations of gypenosides, in C57BL/KSJ-db/db mice. For 5 weeks, animals were provided a standard AIN-76 diet (normal control) with rosiglitazone (0.005%, wt/wt) or two different doses of G. pentaphyllum ethanol extract (GPE) of the plant leaves (0.0025% and 0.01%, wt/wt). After the experimental period, the blood glucose levels of the high-dose GPE- and rosiglitazone-supplemented groups were significantly lower than that of the control group. The plasma insulin concentrations of the GPE-supplemented mice were significantly elevated compared to the control group. The GPE and rosiglitazone treatments profoundly affected the intraperitoneal insulin tolerance test compared to the control group, but not the intraperitoneal glucose tolerance test. In the evaluation of effects on hepatic glucose metabolism, the ratios of glucokinase/glucose-6-phosphatase activities in the high-dose GPE- and rosiglitazone-supplemented groups were prominently higher than that of the control group. The histology of the pancreatic islets revealed that the insulin-positive beta-cell numbers were higher in the high-dose GPE- and rosiglitazone-supplemented groups than in the control group. These results suggest that the supplementation of high-dose GPE (0.01%) in the diet lowers the blood glucose level by altering the hepatic glucose metabolic enzyme activities.

A novel insulin-releasing substance, phanoside, from the plant Gynostemma pentaphyllum.

Author: Norberg A, Hoa NK, Liepinsh E, Van Phan D, Thuan ND, J�rnvall H, Sillard R, Ostenson CG.
Source: J Biol Chem. 2004 Oct 1;279(40):41361-7. Epub 2004 Jun 25.

Extracts from Gynostemma pentaphyllum Makino (Cucurbitaceae), a Southeast Asian herb, has been reported to affect numerous activities resulting in antitumor, cholesterol-lowering, immunopotentiating, antioxidant, and hypoglycemic effects. We have isolated one active compound by ethanol extraction, distribution in n-butyl alcohol/water, solid phase extraction/separation, and several rounds of reverse phase high pressure liquid chromatography. We have shown by NMR and mass spectrometry that this active compound is a novel saponin, a gypenoside, which we have named phanoside (21-,23-epoxy-,3beta-,20-,21-trihydroxydammar-24-ene-3-O-([alpha-d-rhamnopyranosyl(1-->2)]-[beta-d-glycopyranosyl(1-->3)]-beta-d-lyxopyranoside)), with a molecular mass of 914.5 Da. Phanoside is a dammarane-type saponin, and four stereoisomers differing in configurations at positions 21 and 23 were identified, each of which were found to stimulate insulin release from isolated rat pancreatic islets. We have also found that the stereoisomers are interconvertible. Dose-dependent insulin-releasing activities at 3.3 and 16.7 mM glucose levels were determined for the racemic mixture containing all four stereoisomers. Phanoside at 500 microM stimulates insulin release in vitro 10-fold at 3.3 mM glucose and potentiates the release almost 4-fold at 16.7 mM glucose. At these glucose levels, 2 microm glibenclamide stimulates insulin release only 2-fold. Interestingly, beta-cell sensitivity to phanoside is higher at 16.7 mM than at 3.3 mM glucose, although insulin responses were significantly increased by phanoside below 125 microM only at high glucose levels. Also when given orally to rats, phanoside (40 and 80 mg/ml) improved glucose tolerance and enhanced plasma insulin levels at hyperglycemia.

Protein tyrosine phosphatase 1B inhibitory by dammaranes from Vietnamese Giao-Co-Lam tea.

Author: Hung TM, Hoang DM, Kim JC, Jang HS, Ahn JS, Min BS.
Source: J Ethnopharmacol. 2009 Jul 15;124(2):240-5. Epub 2009 May 3.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) tea was used in Vietnamese folk medicine as anti-diabetic agent. AIM OF THE STUDY: This study was aimed to investigate the inhibitory activities of fractions and constituents isolated from Gynostemma pentaphyllum on protein tyrosine phosphatase 1B (PTP1B) since it has been proposed as a treatment therapy for type 2 diabetes and obesity. MATERIALS AND METHODS: The 70% EtOH extract, CHCl3 fraction, EtOAc fraction, BuOH fraction, and seven isolated dammarane triterpenes were evaluated for their inhibitory activity in protein phosphatase enzymes (PTP1B and VHR). RESULTS: CHCl3-soluble fraction showed a dose-dependent inhibitory activity of the PTP1B enzyme with the IC50 value of 30.5 microg/mL. Among seven tested compounds, compounds 6 showed the most potent PTP1B inhibitory activity with IC50 value of 5.3+/-0.4 microM compared to a range 15.7-28.5 microM for the other six compounds. The inhibition mode of 6 was competitive toward p-NPP with a K(i) value of 2.8 microM. CONCLUSION: These study results suggested that the PTP1B inhibitory activity of these dammaranes may enable this plant to play an important role in the treatment of diabetes.
[Phytotherapeutic aspects of diseases of the cardiovascular system. 5. Saponins and possibilities of their use in prevention and therapy]

Author: Purmov� J, Opletal L.
Source: Ceska Slov Farm. 1995 Oct;44(5):246-51. Review. Czech.

The summarizing paper deals with the structure and biological effects of saponins generally and in relation with the treatment and prevention of diseases of the heart and circulatory system. In this field, mainly the saponins from the plants of the genera Panax, Gynostemma or Bupleurum are of use. Also soya saponins and saponins of the genera Astragalus, Salvia, Boussigaultia and Litchi can be employed. Saponins exert a positive effect on the function of the heart direct, or they help treat related diseases. For instance, they inhibit the formation of lipid peroxides in the cardiac muscle or in the liver, they influence the function of enzymes contained in them, they decrease blood coagulation, cholesterol and sugar levels in blood, they stimulate the immunity system. They act either direct, blocking the transfer of Ca2+ ions or modulating the function of Na(+)-K(+)-ATPase, or they help resorb other active principles. It can be concluded that saponins are a prospective group of drugs of natural origin for the prevention and treatment of diseases of the heart and circulatory system.
[Antithrombotic effect of Gynostemma pentaphyllum]

Author: Tan H, Liu ZL, Liu MJ.
Source: Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993 May;13(5):278-80, 261. Chinese.

Human blood samples were investigated in vitro to observe the antithrombotic effect of water extract of Gynostemma pentaphyllum (GP). The results showed that GP could inhibit significantly the platelet aggregation induced by ADP and compound agonists (P < 0.05), accelerate obviously the disaggregation (P < 0.05) and inhibit effectively the experimental thrombosis (P < 0.05). The delayed effects of GP on KPTT, PT, TT, AT, RVV-RT, RVV-CT suggested that this drug could decrease the activity of multiple coagulation factors. And it showed that GP could accelerate the erythrocyte electrophoresis rate. This study revealed that GP is an antithrombotic agent affecting the links of thrombotic chain which is worthwhile to be studied further.
[Effect of total flaveos of Gynostemma pentaphyllum on protein expression of Fas/FasL genes and TNF-alpha concentration in cultured neonatal rat cardiomyocytes with hypoxia-reoxygenation]

Author: Le L, Gao XL, Ding BX, Yuan BX.
Source: Zhongguo Zhong Yao Za Zhi. 2007 Sep;32(18):1925-7. Chinese.

OBJECTIVE: To study the effect of total flaveos of Gymostemma pentaphyllum on the protein expression of apoptosis-associated Fas/FasL gene and tumor necrosis factor-alpha (TNF-alpha) concentration in cultured neonatal rat cardiomyocytes with hypoxia-reoxygenation (H/R). METHOD: A cultured primary neonatal rat cardiomyocytes model with H/R was erected, experiments were divided into six groups, (1)control group, (2)H/R group, (3)15 mg x L(-1) TFG plus H/R group, (4)45 mg x L(-1) TFG plus H/R group, (5) 105 mg x L(-1) TFG plus H/R group, (6)105 mg x L(-1) TFG group. TNF-aconcentration in cultured cardiomyocytes with H/R, was determined by ELISA method, the protein expression of Fas/FasL genes were estimated by immunohisto-chemistry. RESULT: After cardiomyocytes were made with H/R, Compared with control group, the positive expression index (PEI) of Fas/FasL proteins in cardiomyocytes increased significantly, Compared with H/R groups, the PEI of Fas/FasL proteins were lower significantly in groups with different dosages of TFG (P < 0.05). TFG inhibited the secretion of TNF-alpha from myocardial cells and increased the survival rate of myocardial cells. CONCLUSION: The protein expression of apoptosis-associated Fas/FasL genes increased during H/R. The TFG can protect myocardium against H/R injury by decreasing the production of TNF-alpha, downregulating the protein expression of Fas/FasL genes, and then inhibiting myocyte apoptosis.

Cardiovascular effects of the aqueous extract of Gynostemma pentaphyllum Makino.

Author: Circosta C, De Pasquale R, Occhiuto F.
Source: Phytomedicine. 2005 Sep;12(9):638-43.

In the present study, the cardiovascular activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in the anaestetized guinea-pigs and has been compared with two of its isolated gypenosides (III, VIII) and with verapamil, a well-known Ca-antagonistic drug. The results obtained showed that the intravenous administration of the decoction of G. pentaphyllum (2.5, 5 and 10mg/kg) produced a protective effect against pitressin-induced coronaryspasm, arrhythmias and pressor response. Extract also increased the dose of ouabain required to cause ventricular tachyarrhythmias and lethality. Further extract reversed ouabain-induced persistent ventricular tachycardia and restored sinus rhythm in a dose-dependent manner. The results obtained have also shown that gypenosides III and VIII caused similar protective effects in both experimental models used; however, the duration of the action is lower than that of the extract containing corresponding quantities of gypenosides III and VIII.

Haemolytic activities and adjuvant effect of Gynostemma pentaphyllum saponins on the immune responses to ovalbumin in mice.

Author: Sun H, Zheng Q.
Source: Phytother Res. 2005 Oct;19(10):895-900.

In this study, the haemolytic activities of Gynostemma pentaphyllum saponins (GPS) and its adjuvant potential on the immune responses of ICR mice against ovalbumin (OVA) were evaluated. GPS showed a slight haemolytic effect, with its haemolytic activity being 10.20% and 4.90% at concentrations of 500 and 250 microg/mL, respectively. ICR mice were immunized subcutaneously with OVA 100 microg alone or with OVA 100 microg dissolved in saline containing aluminium hydroxide gel (Alum, 200 microg), QuilA (10 and 20 microg) or GPS (50, 100 or 200 microg) on days 1 and 15. Two weeks later (day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-stimulated splenocyte proliferation and OVA-specific antibodies in serum were measured. GPS significantly enhanced the Con A-, LPS- and OVA-induced splenocyte proliferation in the OVA-immunized mice, especially at a dose of 100 microg (p < 0.05 or p < 0.001). OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were also significantly enhanced by GPS compared with the OVA control group (p < 0.05, p < 0.01 or p < 0.001). In conclusion, the results suggest that GPS could be used safely as an adjuvant with low or no haemolytic effect. Copyright (c) 2005 John Wiley & Sons, Ltd.
Immunomodulatory effects of cadmium and Gynostemma pentaphyllum herbal tea on rat splenocyte proliferation.

Author: Suntararuks S, Yoopan N, Rangkadilok N, Worasuttayangkurn L, Nookabkaew S, Satayavivad J.
Source: J Agric Food Chem. 2008 Oct 8;56(19):9305-11. Epub 2008 Sep 17.

Gynostemma pentaphyllum Makino (GP) is a herbal tea widely grown in Southeast Asia. However, this herbal tea can be contaminated with some heavy metals, especially cadmium (Cd), from agricultural areas, which may affect human health. The objective of this study is to evaluate the immunomodulatory effects of Cd contaminated in GP herbal tea and inorganic Cd on rat splenocytes. Rats were divided into groups and treated with drinking water (control), high CdCl 2 in drinking water (HCd; 0.05 mg/L), GP herbal tea containing 0.05 mg/L Cd (GP-HCd) for 4 months, low CdCl 2 in drinking water (LCd; 0.006 mg/L), and GP herbal tea containing 0.006 mg/L Cd (GP-LCd) for 6 months. After the treatments, Cd accumulation in organs and blood was detected by using a graphite furnace atomic absorption spectrophotometer. In spleen, HCd-treated rats had 4-fold higher Cd accumulations than GP-HCd-treated rats. Cd accumulation in liver and kidney in the HCd group also increased significantly. There were no significant changes in total leucocyte and lymphocyte counts; however, these parameters tended to decrease slightly in LCd, GP-LCd, and GP-HCd groups. The HCd group (ex vivo) significantly produced suppressive effects on T cell mitogen-induced splenocyte proliferation, with 1 mug/mL Con A and PHA-P. In addition, 0.5 mug/mL PWM-induced B cell proliferation, through T cell functions, was also significantly inhibited by HCd as compared to the control group, while GP-HCd had no effects. However, both GP-LCd- and LCd-treated rats had a slight increase in Con A-stimulated splenocyte proliferation. This study indicated that high Cd contamination in drinking water alone had suppressive effects on T cell functions, but these effects could not be found with the same Cd level contamination in GP herbal tea.

Isolation and characterization of immunostimulatory polysaccharide from an herb tea, Gynostemma pentaphyllum Makino.

Author: Yang X, Zhao Y, Yang Y, Ruan Y.
Source: J Agric Food Chem. 2008 Aug 27;56(16):6905-9. Epub 2008 Jul 18.

Water-soluble polysaccharide from Gynostemma pentaphyllum herb tea (PSGP) was isolated by hot-water extraction and ethanol precipitation. The chemical components and preliminary immunomodulating activity of PSGP were investigated both in vitro and in vivo. Capillary zone electrophoresis analysis showed that PSGP was a typical nonstarch heteropolysaccharide, with glucose being the main component monosaccharide (23.2%), followed by galactose (18.9%), arabinose (10.5%), rhamnose (7.7%), galacturonic acid (4.7%), xylose (3.9%), mannose (3.1%), and glucuronic acid (1.2%). PSGP could significantly stimulate peritoneal macrophages to release nitric oxide, reactive oxygen species, and tumor necrosis factor-alpha in a dose-dependent manner. This immunostimulating activity of PSGP was further demonstrated by its inhibition on the proliferation of human colon carcinoma HT-29 and SW-116 cells incubated with the supernatant of PSGP-stimulated macrophage culture. It is evident that PSGP is a very important ingredient responsible for at least in part the immunomodulating activity of G. pentaphyllum herb tea.
Extract of Gynostemma pentaphyllum enhanced the production of antibodies and cytokines in mice.

Author: Huang WC, Kuo ML, Li ML, Yang RC, Liou CJ, Shen JJ.
Source: Yakugaku Zasshi. 2007 May;127(5):889-96.

Gynostemma pentaphyllum is a popular herbal tea in China and some Asian countries. The modulatory function of G. pentaphyllum total plant extracts on immune cells was evaluated in this study. The extract was intraperitoneally injected into mice for 5 consecutive days. The production of antibodies from B cells or cytokines from T cells was determined mainly with ELISA. After the treatment, serum IgM and IgG2a were significantly enhanced and showed dose-dependent effect. Moreover, serum IgA and IgG1 were also increased when received the extract at the doses of 0.05 or 0.50 g/kg/day. In addition to the serum levels, the injection of the extract enhanced the production of all antibodies from LPS-activated spleen cells. Furthermore, more cytokines were secreted from Con A-stimulated splenocytes of G. pentaphyllum-treated mice. Our results suggest that the extract of G. pentaphyllum might promote immune responses through the activation of T and B cells.
[Immunomodulatory action of the total saponin of Gynostemma pentaphyllum]

Author: Zhang C, Yang X, Xu L.
Source: Zhong Xi Yi Jie He Za Zhi. 1990 Feb;10(2):96-8, 69-70. Chinese.

The specimen of the total saponin for this experimental study was extracted from Gynostemma pentaphylla growing in Suining county in Hunan province. Weight of immune organs, content of anti-SRBC hemolysin, rate of special Ea-RFC formation and percentage of NK cell activity had been employed for the study as experimental indices, both the normal healthy mice and the mice with immunity impairment due to Cyclophosphamide (Cy) management as experimental models. The results of the study exhibited: (1) The total saponin of Gynostemma pentaphylla could markedly act against the immunity inhibition due to Cy management in the experimental animals, showing a variant recovery in mice treated by Cy in weight of the immune organs, content of hemolysin, forming rate of Ea-RFC and unequivocally elevating NK cell activity, by significant difference in comparison with the Cy control groups (P less than 0.05-0.01). (2) The total saponin showed a definite of bidirective immunomodulatory action in normal healthy mice, recovering the immune indices to normal value from either originally lower or higher than the medium figure, by significant difference in comparison with the Cy control groups (P less than 0.05-0.01). (3) The total saponin had actions to prevent from fatigue and to tolerate hypoxia under usual atmospheric pressure. The above description indicates that the total saponin of Gynostemma pentaphylla is a better immunomodulator, seems to be like the actions of some Chinese drugs, for example, Panax ginseng, Astragalus membranaceus etc.
Gypenoside XLIX, a naturally occurring gynosaponin, PPAR-alpha dependently inhibits LPS-induced tissue factor expression and activity in human THP-1 monocytic cells.

Author: Huang TH, Tran VH, Roufogalis BD, Li Y.
Source: Toxicol Appl Pharmacol. 2007 Jan 1;218(1):30-6. Epub 2006 Oct 25.

Tissue factor (TF) is involved not only in the progression of atherosclerosis and other cardiovascular diseases, but is also associated with tumor growth, metastasis, and angiogenesis and hence may be an attractive target for directed cancer therapeutics. Gynostemma pentaphyllum (GP) is widely used in the treatment of various cardiovascular diseases including atherosclerosis, as well as cancers. Gypenoside (Gyp) XLIX, a dammarane-type glycoside, is one of the prominent components in GP. We have recently reported Gyp XLIX to be a potent peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gyp XLIX (0-300 microM) concentration dependently inhibited TF promoter activity after induction by the inflammatory stimulus lipopolysaccharide (LPS) in human monocytic THP-1 cells transfected with promoter reporter constructs pTF-LUC. Furthermore, Gyp XLIX inhibited LPS-induced TF mRNA and protein overexpression in THP-1 monocyte cells. Its inhibition of LPS-induced TF hyperactivity was further confirmed by chromogenic enzyme activity assay. The activities of Gyp XLIX reported in this study were similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, the Gyp XLIX-induced inhibitory effect on TF luciferase activity was completely abolished in the presence of the PPAR-alpha selective antagonist MK-886. The present findings suggest that Gyp XLIX inhibits LPS-induced TF overexpression and enhancement of its activity in human THP-1 monocytic cells via PPAR-alpha-dependent pathways. The data provide new insights into the basis of the use of the traditional Chinese herbal medicine G. pentaphyllum for the treatment of cardiovascular and inflammatory diseases, as well as cancers.


Gypenoside XLIX isolated from Gynostemma pentaphyllum inhibits nuclear factor-kappaB activation via a PPAR-alpha-dependent pathway.

Author: Huang TH, Li Y, Razmovski-Naumovski V, Tran VH, Li GQ, Duke CC, Roufogalis BD.
Source: J Biomed Sci. 2006 Jul;13(4):535-48. Epub 2006 Mar 10.

Nuclear factor (NF)-kappaB is important in the generation of inflammation. Besides regulating lipid metabolism, peroxisome proliferator-activated receptor (PPAR)-alpha activators also reduce NF-kappaB activation to terminate activation of inflammatory pathways. Gynostemma pentaphyllum (GP) has been used to treat various inflammatory diseases and hyperlipidemia. Here, we demonstrate that GP extract and one of its main components, Gypenoside XLIX (Gyp-XLIX) inhibited LPS-induced NF-kappaB activation in murine macrophages. Furthermore, Gyp-XLIX restored the LPS- and TNF-alpha-induced decrease in cytosolic I-kappaBalpha protein expression and inhibited the translocation of NF-kappaB(p65) to the nucleus in THP-1 monocyte and HUVEC cells. The inhibition of LPS- and TNF-alpha-induced NF-kappaB luciferase activity in macrophages was abolished by MK-886, a selective PPAR-alpha antagonist. GP extract and Gyp-XLIX (EC(50): 10.1 microM) enhanced PPAR-alpha luciferase activity in HEK293 cells transfected with the tK-PPREx3-Luc reporter plasmid and expression vectors for PPAR-alpha. Additionally, Gyp-XLIX specifically enhanced PPAR-alpha mRNA and protein expression in THP-1-derived macrophage cells. The selectivity of Gyp-XLIX for PPAR-alpha was demonstrated by the activation of only PPAR-alpha in HEK293 cells transfected with expression vectors for PPAR-alpha, PPAR-beta/delta or PPAR-gamma1 plasmids and in THP-1-derived macrophage naturally expressing all three PPAR isoforms. The present study demonstrates that Gyp-XLIX, a naturally occurring gynosaponin, inhibits NF-kappaB activation via a PPAR-alpha-dependent pathway.

Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF-kappaB-mediated iNOS protein expression.

Author: Aktan F, Henness S, Roufogalis BD, Ammit AJ.
Source: Nitric Oxide. 2003 Jun;8(4):235-42.

Gypenosides isolated from Gynostemma pentaphyllum are widely used in traditional Chinese medicine, with beneficial effects reported in numerous diseases, including inflammation and atherosclerosis, although the mechanism underlying these therapeutic effects is unknown. Because increased nitric oxide (NO) plays a role in these pathological conditions, we investigated whether the pharmacological activity of gypenosides is due to suppression of NO synthesis. The markedly increased production of nitrite by stimulation of RAW 264.7 murine macrophages with 1 microg/mL lipopolysaccharide (LPS) for 20 h (unstimulated: 0.3+/-0.3 microM vs. LPS: 32.5+/-1.2 microM) was dose-dependently inhibited by gypenosides (0.1-100 microg/mL). When cells were pretreated with gypenosides (for 1h) prior to LPS stimulation, subsequent NO production was significantly attenuated (IC(50) of 3.1+/-0.4 microg/mL) (P<0.05). Gypenosides (25 microg/mL) produced the same maximum inhibition of LPS-induced NO production as aminoguanidine, a standard inhibitor of NOS enzymes. Suppression of NO production occurred both by direct inhibition of the activity and expression of iNOS. Inhibition of iNOS protein expression appears to be at the transcriptional level, since gypenosides decreased LPS-induced NF-kappaB activity in a dose-dependent manner (P<0.05), with significant inhibition achieved following pretreatment with 10 microg/mL gypenoside. Taken together, these results suggest that gypenosides derived from G. pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF-kappaB-mediated iNOS protein expression, thereby implicating a mechanism by which gypenosides may exert their therapeutic effects.

Gypenoside XLIX, a naturally occurring PPAR-alpha activator, inhibits cytokine-induced vascular cell adhesion molecule-1 expression and activity in human endothelial cells.

Author: Huang TH, Tran VH, Roufogalis BD, Li Y.
Source: Eur J Pharmacol. 2007 Jun 22;565(1-3):158-65. Epub 2007 Mar 24.

Vascular cell adhesion molecule-1 (VCAM-1) is involved in several diseases, including chronic inflammation and atherosclerosis. Inhibition of the expression of this adhesion molecule is one of the key targets of anti-inflammatory, anti-cancer and anti-atherosclerotic drugs. Gynostemma pentaphyllum is a traditional medicine widely used in the treatment of respiratory inflammation, hyperlipidemia and atherosclerosis. However, its molecular mechanisms of action are still largely unknown. Gypenoside XLIX, a dammarane-type glycoside, is a prominent component of G. pentaphyllum. We have recently demonstrated Gypenoside XLIX to be a selective peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gypenoside XLIX concentration-dependently (0-300 microM) inhibited VCAM-1 promoter activity after induction by cytokine tumor necrosis factor (TNF)-alpha in human umbilical vein endothelial cells (HUVECs) transfected with promoter-reporter construct pVCAM-1-LUC. Furthermore, Gypenoside XLIX inhibited TNF-alpha-induced VCAM-1 mRNA and protein overexpression in HUVECs. The result of the enzyme immunoassay demonstrated that Gypenoside XLIX inhibited TNF-alpha-induced increase in cell surface VCAM-1 protein levels in HUVECs. In the present study we show that activities of Gypenoside XLIX are similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, Gypenoside XLIX-induced inhibition on TNF-alpha-stimulated VCAM-1 promoter hyperactivity was completely abolished by a selective blocker of PPAR-alpha, MK-886. Thus, our findings suggest that Gypenoside XLIX inhibits cytokine-induced VCAM-1 overexpression and hyperactivity in human endothelial cells via a PPAR-alpha-dependent pathway. These data provide new insight into the rational basis of the use of the traditional Chinese herbal medicine G. pentaphyllum in the treatment of inflammatory and cardiovascular diseases, including atherosclerosis.

Liver Injury and Disease

Therapeutic effect of gypenoside on chronic liver injury and fibrosis induced by CCl4 in rats.

Author: Chen JC, Tsai CC, Chen LD, Chen HH, Wang WC.
Source: Am J Chin Med. 2000;28(2):175-85.

Gypenoside is a saponins extract derived from the Gynostemma pentaphyllum. The purpose of this study was to evaluate the hepatoprotective and antifibrotic potential of Gypenoside on chronic liver injury induced by CCl4 for 8 wks. The results indicated that the increase of SGOT, SGPT activities in CCl4 liver injury were significantly reduced by treatment with Gypenoside. It also elevated the A/G ratio. For the study of anti-fibrotic potential, Gypenoside reduced the collagen content by 33%. These phenomena were confirmed by pathologic observation; thinner bands of liver collagen were found. The results suggest that Gypenoside has hepatoprotective and anti-fibrotic activities.

The add-on effects of Gynostemma pentaphyllum on nonalcoholic fatty liver disease.

Author: Chou SC, Chen KW, Hwang JS, Lu WT, Chu YY, Lin JD, Chang HJ, See LC.
Source: Altern Ther Health Med. 2006 May-Jun;12(3):34-9.

CONTEXT: Other than weight reduction by dieting or physical activity, there are no well-documented medical treatments for fatty liver disease. OBJECTIVE: To evaluate the efficacy of the add-on Gynostemma pentaphyllum (GP) in research subjects with nonalcoholic fatty liver disease. DESIGN: A randomized, single-blind, controlled clinical trial. SETTING: Hospital-based clinic. PATIENTS: Fifty-six research subjects who were diagnosed with nonalcoholic fatty liver by abdominal ultrasound scanning. INTERVENTIONS: The treatment group and the control group followed a controlled diet for 2 months. After 2 months, the treatment group continued to diet and received 80 mL GP extraction for 4 months; the control group continued to diet and received a placebo capsule for 4 months. MAIN OUTCOME MEASURES: Body mass index (BMI), biochemistry data, and fatty liver score were measured at baseline, at 2 months, and at 6 months. RESULTS: After 2 months of dieting, BMI and most biochemistry data decreased in both study groups. There were no significant differences in BMI or biochemistry data at month 2 between the 2 study groups. At month 6, BMI, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, insulin (ALP), insulin resistance index (HOMA-IR), and fatty liver score were reduced in both groups. The treatment group saw significant reductions in BMI, AST, ALP, insulin, and HOMA-IR, however. Changes in uric acid levels in the 2 groups from month 2 to month 6 were statistically significant (P = .028) CONCLUSION: GP is an effective adjunct treatment to diet therapy for patients with nonalcoholic fatty liver disease.

Evaluation of the anti-inflammatory and liver-protective effects of anoectochilus formosanus, ganoderma lucidum and Gynostemma pentaphyllum in rats.

Author: Lin JM, Lin CC, Chiu HF, Yang JJ, Lee SG.
Source: Am J Chin Med. 1993;21(1):59-69.

The pharmacological effects of Anoectochilus formosanus, Ganoderma lucidum and Gynostemma pentaphyllum were studied against carrageenan-induced paw edema and CC1(4)-induced hepatotoxicity in rats. The water extracts of G. pentaphyllum and G. lucidum were found to possess significant anti-inflammatory activity against carrageenan induced edema. The administration of Gynostemma pentaphyllum displayed an activity even more potent than indomethacin. In contrast, Anoectochilus formosanus showed a delayed onset of anti-inflammatory activity starting from 4 hrs post carrageenan administration. However, A. formosanus significantly decreased the acute increase in serum GOT and GPT level caused by CC1(4). Histological changes such as necrosis, fatty change, ballooning degeneration, inflammatory infiltration of lymphocytes and Kupffer cells around the central vein were simultaneously improved by the treatment of A. formosanus.

Radiation Protection


Inhibitory effects of Gynostemma pentaphyllum on the UV induction of bacteriophage lambda in lysogenic Escherichia coli.

Author: Zhu S, Fang C, Zhu S, Peng F, Zhang L, Fan C.
Source: Curr Microbiol. 2001 Oct;43(4):299-301.

Effects of gynostemma pentaphyllum (GP) on the bacteriophage lambda induced by ultraviolet (UV) irradiation have been studied. The results showed that GP could inhibit the UV induction of bacteriophage lambda in lysogenic cells. The inhibitory effects were dependent on the concentration and the reaction time of GP, and were efficient at 40 to approximately 125 microg ml(-1) for 10 min. The inhibitory rate was higher than 70% when the GP concentration was 50 microg ml(-1). By electron spin resonance (ESR) and spin-trapping techniques, the signals of free radicals were detected in the suspension of the lambda lysogenic bacteria induced by ultraviolet irradiation, but after the addition of GP the signals were decreased. These results indicate that gynostemma pentaphyllum not only is a scavenger of free radicals, but also possesses the biological function of anti-irradiation, and that there is a close relation between the UV irradiation of the bacteriaphage lambda and free radicals.


Protective effects of Gynostemma pentaphyllum in gamma-irradiated mice.

Author: Chen WC, Hau DM, Chen KT, Wang MI, Lin IH.
Source: Am J Chin Med. 1996;24(1):83-92. Erratum in: Am J Chin Med 1996;24(2):204.

Radiation protective effects of Gynostemma Pentaphyllum (Gp) were investigated in gamma-irradiated mice. Animals were sacrificed on days 5, 15, 25 and 35 after gamma-irradiation. GOT, GPT, serum IgG and leukocyte counts were measured. Proliferation of splenocytes stimulated by mitogens, such as PHA, Con A, and LPS were detected and compared. The results showed that all parameters measured in this study were decreased and proliferation of splenocytes stimulated by mitogens were repressed in gamma-irradiated mice. Gp helped to recover the decreased leukocyte counts, GOT, GPT and IgG in serum and the proliferation of splenocytes stimulated by PHA, LPS and Con A in the gamma-ray irradiated mice.


STROKE

Management of SAH with traditional Chinese medicine in China.

Author: Wang C, Zhao X, Mao S, Wang Y, Cui X, Pu Y.
Source: Neurol Res. 2006 Jun;28(4):436-44. Review.

China lacks large scale authorized epidemiological study results in allusion to subarachnoid hemorrhage (SAH) within recent 15 years since MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study revealed SAH situation in China in 2000. The main cause of SAH in China is aneurysm which takes up 30-50%, while over 90% aneurysm locates at Willis circle. Early surgery for SAH after aneurysm rupture is the dominant procedure to deal with SAH in China. Moreover, calcium antagonists rank the absolute leading position for cerebral vascular spasm (CVS) among medication-based treatment options. However, traditional Chinese medicine such as Salvia miltiorrhiza, Acanthopanax senticosus, Ginkgo biloba, Pueraria lobata, Liguisticum chuanxiong, cow bezoar, Diospyros kaki and Gynostemma pentaphyllum have been proven beneficial in CVS prevention and treatment, while Salvia miltiorrhiza and TCM soup have unique effects on bleeding absorption. In addition, aescine and some TCM soup might relieve strong headache after SAH. In general, TCM integrated with western medicine have shown unique advantages in the current treatment of SAH in China. However, it is a pity that China still lacks larger scale randomized controlled trials and research on SAH treatment focusing on TCM and the related mechanism of TCM on SAH still need to be investigated further.

[Antithrombotic effect of Gynostemma pentaphyllum]

Author: Tan H, Liu ZL, Liu MJ.
Source: Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993 May;13(5):278-80, 261. Chinese.

Human blood samples were investigated in vitro to observe the antithrombotic effect of water extract of Gynostemma pentaphyllum (GP). The results showed that GP could inhibit significantly the platelet aggregation induced by ADP and compound agonists (P < 0.05), accelerate obviously the disaggregation (P < 0.05) and inhibit effectively the experimental thrombosis (P < 0.05). The delayed effects of GP on KPTT, PT, TT, AT, RVV-RT, RVV-CT suggested that this drug could decrease the activity of multiple coagulation factors. And it showed that GP could accelerate the erythrocyte electrophoresis rate. This study revealed that GP is an antithrombotic agent affecting the links of thrombotic chain which is worthwhile to be studied further.

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