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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 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.
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