Ginsenoside-Rg1 (G-Rg1), a saponin that is a primary component of ginseng, is effective against inflammatory diseases. The P2X purinoceptor 7 (P2X7) receptor is an ATP-gated ion channel that is predominantly expressed in immune cells and plays a key role in inflammatory processes. We investigated the role of G-Rg1 in sepsis-related cardiac dysfunction and the underlying mechanism involving the regulation of the P2X7 receptor. We detected cell viability, cytotoxicity, cellular reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) with or without G-Rg1 in lipopolysaccharide (LPS)- or hypoxia/reoxygenation (H/R)-induced H9c2 cell models of ischemia/reperfusion injury. We applied cecal ligation and puncture (CLP) to induce a mouse model of sepsis and measured the survival duration and cardiac function of CLP mice. Next, we quantified the ROS level, MMP, respiratory chain complex I–IV enzymatic activity, and mitochondrial fusion in CLP mouse heart tissues. We then investigated the role of G-Rg1 in repairing LPS-induced cell mitochondrial damage, including mitochondrial superoxidation products. The results showed that G-Rg1 inhibited LPS- or H/R-induced cardiomyocyte apoptosis, cytotoxicity, ROS levels, and mitochondrial damage. In addition, G-Rg1 prolonged the survival time of CLP mice. G-Rg1 attenuated LPS-induced superoxide production in the mitochondria of cardiomyocytes and the excessive release of cytochrome c from mitochondria into the cytoplasm. Most importantly, G-Rg1 suppressed LPS-mediated induction of proapoptotic Bax, activated Akt, induced GSK-3β phosphorylation, and balanced mitochondrial calcium levels. Overall, G-Rg1 activates the Akt/GSK-3β pathway through P2X7 receptors to inhibit sepsis-induced cardiac dysfunction and mitochondrial dysfunction.

中文翻译：

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人参皂甙-Rg1 通过 P2X7 受体介导的 Akt/GSK-3β 信号通路调节线粒体损伤，减轻脓毒症引起的心功能不全

人参皂甙-Rg1 (G-Rg1) 是一种皂苷，是人参的主要成分，对炎症性疾病有效。P2X 嘌呤受体 7 (P2X7) 受体是一种 ATP 门控离子通道，主要在免疫细胞中表达，在炎症过程中起关键作用。我们研究了 G-Rg1 在脓毒症相关心脏功能障碍中的作用以及涉及 P2X7 受体调节的潜在机制。我们在脂多糖 (LPS) 或缺氧/复氧 (H/R) 诱导的 H9c2 细胞模型中检测了有或没有 G-Rg1 的细胞活力、细胞毒性、细胞活性氧 (ROS) 水平和线粒体膜电位 (MMP)缺血/再灌注损伤。我们应用盲肠结扎和穿刺 (CLP) 来诱导败血症小鼠模型并测量 CLP 小鼠的存活时间和心脏功能。下一个，我们量化了 CLP 小鼠心脏组织中的 ROS 水平、MMP、呼吸链复合物 I-IV 酶活性和线粒体融合。然后我们研究了 G-Rg1 在修复 LPS 诱导的细胞线粒体损伤中的作用，包括线粒体超氧化产物。结果表明，G-Rg1 抑制 LPS 或 H/R 诱导的心肌细胞凋亡、细胞毒性、ROS 水平和线粒体损伤。此外，G-Rg1 延长了 CLP 小鼠的存活时间。G-Rg1 减弱了 LPS 诱导的心肌细胞线粒体中超氧化物的产生以及细胞色素 c 从线粒体过度释放到细胞质中。最重要的是，G-Rg1 抑制 LPS 介导的促凋亡 Bax 诱导、激活 Akt、诱导 GSK-3β 磷酸化和平衡线粒体钙水平。全面的，