Gypenosides alleviate myocardial ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function in rat heart

Abstract

Gypenosides (GP) are the predominant components of Gynostemma pentaphyllum, a Chinese herb medicine that has been widely used for the treatment of chronic inflammation, hyperlipidemia, and cardiovascular disease. GP has been demonstrated to exert protective effects on the liver and brain against ischemia-reperfusion (I/R) injury, yet whether it is beneficial to the heart during myocardial I/R is unclear. In this study, we demonstrate that pre-treatment with GP dose-dependently limits infarct size, alleviates I/R-induced pathological changes in the myocardium, and preserves left ventricular function in a rat model of cardiac I/R injury. In addition, GP pre-treatment reduces oxidative stress and protects the intracellular antioxidant machinery in the myocardium. Further, we show that the cardioprotective effect of GP is associated with the preservation of mitochondrial function in the cardiomyocytes, as indicated by ATP level, enzymatic activities of complex I, II, and IV on the mitochondrial respiration chain, and the activity of citrate synthase in the citric acid cycle for energy generation. Moreover, GP maintains mitochondrial membrane integrity and inhibits the release of cytochrome c from the mitochondria to the cytosol. The cytoprotective effect of GP is further confirmed in vitro in H9c2 cardiomyoblast cell line with oxygen-glucose deprivation and reperfusion (OGD/R), and the results indicate that GP protects cell viability, reduces oxidative stress, and preserves mitochondrial function. In conclusion, our study suggests that GP may be of clinical value in cytoprotection during acute myocardial infarction and reperfusion.

Gypenosides Prevent H2O2-Induced Retinal Ganglion Cell Apoptosis by Concurrently Suppressing the Neuronal Oxidative Stress and Inflammatory Response

“…We examined cell viability under conditions of oxidative stress and found that 50-200 μM Gp significantly increased the viability of RGC cultures exposed to H 2 O 2 . Our results were consistent with previous studies, which show that Gp reduced ROS levels during ischemia-reperfusion injury, and protect RGCs from oxidative stress in a concentration-dependent manner (Yu et al 2016a).…”

Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety

“…In this regard, the maintenance of the mitochondrial membrane integrity inhibited the release of cytochrome c from the mitochondria into the cytosol. This further demonstrated the role of gypenosides from G. pentaphyllum as a cytoprotective agent against acute myocardial infarction and reperfusion injury (Yu et al, 2016a).…”

<p>Formulation design, characterization, and in vitro and in vivo evaluation of nanostructured lipid carriers containing a bile salt for oral delivery of gypenosides</p>

“…GPS is a bioactive component with various pharmacological properties and beneficial clinical effects on conditions including hyperlipoproteinemia, 1 cancer, [2][3][4] hepatitis, 5 and cardiovascular disease. 6 However, like other saponins, GPS are easily degraded due to their sensitivity to environmental factors, such as heat, light, and oxygen and are limited in their bioavailability and clinical applications owing to their poor lipid and water solubilities and hemolytic properties. Recent studies have focused on strategies to enhance the stability and bioavailability of GPS, which include the use of microcapsules and liposomes.…”