20(S)-Ginsenoside Rg2 attenuates myocardial ischemia/reperfusion injury by reducing oxidative stress and inflammation: role of SIRT1.

Previously we demonstrated that 20(S)-ginsenoside Rg2 protects cardiomyocytes from H2O2-induced injury by inhibiting reactive oxygen species (ROS) production, increasing intracellular levels of antioxidants and attenuating apoptosis. We explored the protective effect of 20(S)-ginsenoside Rg2 on myocardial ischemia/reperfusion (MI/R) injury and to clarify its potential mechanism of action. Rats were exposed to 20(S)-ginsenoside Rg2 in the presence/absence of the silent information regulator SIRT(1) inhibitor EX527 and then subjected to MI/R. 20(S)-Ginsenoside Rg2 conferred a cardioprotective effect by improving post-ischemic cardiac function, decreasing infarct size, reducing the apoptotic index, diminishing expression of creatine kinase-MB, aspartate aminotransferase and lactate dehydrogenase in serum, upregulating expression of SIRT1, B-cell lymphoma-2, procaspase-3 and procaspase-9, and downregulating expression of Bax and acetyl (Ac)-p53. Pretreatment with 20(S)-ginsenoside Rg2 also resulted in reduced myocardial superoxide generation, gp91phox expression, malondialdehyde content, cardiac pro-inflammatory markers and increased myocardial activities of superoxide dismutase, catalase and glutathione peroxidase. These results suggested that MI/R-induced oxidative stress and inflammation were attenuated significantly by 20(S)-ginsenoside Rg2. However, these protective effects were blocked by EX527, indicating that SIRT1 signaling may be involved in the pharmacological action of 20(S)-ginsenoside Rg2. Our results demonstrated that 20(S)-ginsenoside Rg2 attenuates MI/R injury by reducing oxidative stress and inflammatory responses via SIRT1 signaling. 20(S)-Ginsenoside Rg2 confers a protective effect against MI/R injury via SIRT1 signaling, by alleviating oxidative stress and reducing myocardium inflammation.

先前我们证明了20(S)-人参皂苷Rg2通过抑制活性氧（ROS）产生、提高细胞内抗氧化剂水平以及减轻细胞凋亡，保护心肌细胞免受过氧化氢诱导的损伤。我们探究了20(S)-人参皂苷Rg2对心肌缺血/再灌注（MI/R）损伤的保护作用，并阐明其潜在作用机制。大鼠在有/无沉默信息调节因子SIRT(1)抑制剂EX527的情况下接受20(S)-人参皂苷Rg2处理，然后进行MI/R操作。20(S)-人参皂苷Rg2通过改善缺血后心脏功能、减小梗死面积、降低细胞凋亡指数、减少血清中肌酸激酶 - MB、天冬氨酸氨基转移酶和乳酸脱氢酶的表达、上调SIRT1、B细胞淋巴瘤 - 2、半胱天冬酶 - 3原和半胱天冬酶 - 9原的表达以及下调Bax和乙酰化（Ac）-p53的表达，发挥心脏保护作用。用20(S)-人参皂苷Rg2预处理还导致心肌超氧化物产生减少、gp91phox表达降低、丙二醛含量减少、心脏促炎标志物减少以及心肌超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性增加。这些结果表明，20(S)-人参皂苷Rg2显著减轻了MI/R诱导的氧化应激和炎症。然而，这些保护作用被EX527阻断，这表明SIRT1信号通路可能参与20(S)-人参皂苷Rg2的药理作用。我们的结果证明，20(S)-人参皂苷Rg2通过SIRT1信号通路减轻氧化应激和炎症反应，从而减轻MI/R损伤。 20(S)-人参皂苷Rg2通过SIRT1信号通路减轻氧化应激和减少心肌炎症，对MI/R损伤产生保护作用。