Gynostemma Pentaphyllum Extract Research Articles

Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract

Hepatocytes of a primary cell culture that are exposed to high glucose, insulin, and linoleic (LA) acid concentration respond with lipid accumulation, oxidative stress up to cell death. Such alterations are typically found in patients with non-alcoholic fatty liver disease (NAFLD). We used this cellular model to study the effect of an ethanolic Gynostemma pentaphyllum (GP) extract in NAFLD. When hepatocytes were cultured in the presence of high insulin, glucose, and LA concentration the extract completely protected the cells from cell death. In parallel, the extract prevented accumulation of triglycerides (TGs) and cholesterol as well as oxidative stress. Our data further demonstrate that GP stimulates the production of nitric oxide (NO) in hepatocytes and affects the molecular composition of the mitochondrial phospholipid cardiolipin (CL). We conclude that GP is able to protect hepatocytes from cell death, lipid accumulation, and oxidative stress caused by diabetic-like metabolism and lipotoxicity. Therefore, GP could be beneficial for patients with diabetes mellitus and NAFLD.

Long-term oral administration of Gynostemma pentaphyllum extract attenuates airway inflammation and Th2 cell activities in ovalbumin-sensitized mice

Our previous report demonstrated that the oral administration of short-term high dose Gynostemma pentaphyllum extract (5g/kg per day for 7days) decreased allergic reactions in ovalbumin (OVA)-sensitized mice. The aim of this study was to determine whether long-term oral administration of G. pentaphyllum attenuated airway inflammation in OVA-sensitized mice.Mice were sensitized and challenged with normal saline or OVA. OVA-sensitized mice were fed with 1.75g/kg (low dose, GPL) or 5g/kg (high dose, GPH) G. pentaphyllum extract, five days a week for 4weeks. The airway hyperresponsiveness (AHR) and eosinophilia in bronchoalveolar lavage fluid (BALF) were examined. The cytokine levels or antibodies in BALF, serum and spleen cell culture supernatants were also determined. Both high and low dose extracts reduced AHR, serum OVA–IgE, and Th2-associated cytokine levels in spleen cell supernatants and BALF in OVA-sensitized mice. These results show that long-term orally administered G. pentaphyllum extract reduced allergic reactions in OVA-sensitized mice.

Selective induction of apoptosis in glioma tumour cells by a Gynostemma pentaphyllum extract

At low concentration H(2)O(2) is an important signal molecule in proliferation of tumour cells. We report about a study investigating the effect of an ethanolic extract from Gynostemma pentaphyllum on proliferation of C6 glioma tumour cells and cellular H(2)O(2) concentration. The proliferation of these cells was maximal at about 1 muM extracellular H(2)O(2). HPLC-finger prints of the extract revealed a set of saponines as essential components. In C6 glioma cells the extract caused increase in super oxide dismutase (SOD) activity, in the amount of SOD protein, and in cellular H(2)O(2) concentration. It inhibited cell proliferation and induced activation of caspase 3 as indication of apoptosis. No effect of the extract was observed on the proliferation of astrocytes of a primary cell culture. From these findings we suggest that the ethanolic extract from Gynostemma pentaphyllum may selectively shift the H(2)O(2) concentration to toxic levels exclusively in tumour cells due to increased SOD activity. It may have a high potency in cancer therapy and cancer prophylaxis.

The inhibitory effect of Gynostemma pentaphyllum on MCP-1 and type I procollagen expression in rat hepatic stellate cells

Aim of the study Gynostemma pentaphyllum is a popular folk medicine that has been used for treatment of hepatitis in Asia. Our previous study demonstrates that Gynostemma pentaphyllum n-butanol extract inhibits the onset and improves the recovery of CCl 4-induced liver fibrogenesis in rats and inhibits PDGF-induced rat hepatic stellate cells (HSCs) proliferation. In this study, the effect of Gynostemma pentaphyllum extract on cytokines and type I procollagen expression was analyzed. Materials and methods Rat HSCs were treated with PDGF, Gynostemma pentaphyllum n-butanol extract, RP-18-Gyp fraction, rapamycin or vehicle. Rat cytokine antibody array chip or ELISA kit was used for cytokines detection. Intracellular protein expression was detected by Western blotting, mRNA expression was analyzed by RT-PCR. Results RP-18-Gyp fraction is the more purified gypenosides fraction from Gynostemma pentaphyllum n-butanol extract. In cell proliferation, the inhibitory effect of 200 μg/ml RP-18-Gyp fraction is similar to 500 μg/ml Gynostemma pentaphyllum n-butanol extract. Furthermore, both of them have the ability of decreasing monocyte chemoattractant protein-1 (MCP-1) mRNA expression and protein release and inhibiting type I procollagen protein expression. Conclusions Both of Gynostemma pentaphyllum n-butanol extract and its more purified RP-18-Gyp fraction have the biological activities in the inhibition of cell proliferation, MCP-1 release and type I procollagen expression in rat HSCs. These data could provide the evidence to support for the traditional use of Gynostemma pentaphyllum in hepatitis.

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

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.

Specific reversal of multidrug resistance to colchicine in CEM/VLB100 cells by Gynostemma pentaphyllum extract

P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR) is perhaps the most thoroughly studied cellular mechanism of cytotoxic drug resistance. Its efflux function can be circumvented by a wide range of pharmacological agents in vitro and in vivo. Most of these agents are pharmaceuticals used clinically for conditions other than cancer. However, their use in alleviating MDR is limited because the concentrations required for inhibition of the pump surpass their dose-limiting toxicity. The aim of this research is to study the role of gypenosides, isolated from Gynostemma pentaphyllum, as modulators of P-gp-mediated MDR in tumor cells, at both cellular and plasma membrane level. In the presence of total gypenoside preparation (0.1 mg/ml), an approximately 15-fold reversal of colchicine (COL) resistance was observed in P-gp-overexpressed CEM/VLB(100) cells. However, the gypenoside sample showed no reversal effect in cells treated with vinblastine and taxol. A purified gypenoside sample (gypenoside fraction 100) exhibited even more significant reversal of COL resistance (approximately 42-fold) in the CEM/VLB(100) cells. Further examination of the reversal effect of fraction 100 in membrane vesicles derived from CEM/VLB(100) cells using the continuous fluorescence method found that gypenoside fraction 100 at 0.1 mg/ml completely abolished the transport of fluorescein-COL.

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

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.