Non-alcoholic steatohepatitis (NASH) has become the most important reason of liver disease around the world and is predisposed to further progression to cirrhosis and hepatocellular carcinoma. Ginsenoside Rk3 has been reported to have a plenty of biological activities, including anti-apoptotic, anti-anemia, and protective effects against acute kidney injury. However, whether ginsenoside Rk3 can improve NASH has not been reported yet. Therefore, the purpose of this study is to investigate the protective effect of ginsenoside Rk3 against NASH and its mechanism of action. C57BL/6 mice were treated with different dosages of ginsenoside Rk3 after being established as a NASH model. Our results showed that Rk3 administration significantly improved liver inflammation, lipid deposition, and fibrosis caused by a high-fat-high-cholesterol (HFHC) diet and CCl₄ injection in mice. Notably, ginsenoside Rk3 was discovered significantly to inhibit the PI3K/AKT signaling pathway. Additionally, treatment with ginsenoside Rk3 remarkably amended the abundance of short-chain fatty acids. These changes were associated with beneficial variations to the variety and composition of the intestinal microbiota. In conclusion, ginsenoside Rk3 ameliorates hepatic non-alcoholic lipid inflammation and triggers changes in the beneficial intestinal flora, helping to reveal host–microbe interactions. The outcomes of this study indicate that ginsenoside Rk3 is a promising drug candidate for the treatment of NASH.

中文翻译：

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人参皂苷 Rk3 通过调节 C57BL/6 小鼠肠道菌群和 PI3K/AKT 信号通路调节非酒精性脂肪性肝炎

非酒精性脂肪性肝炎（NASH）已成为全世界肝病的最重要原因，并容易进一步进展为肝硬化和肝细胞癌。据报道，人参皂苷 Rk3 具有多种生物活性，包括抗细胞凋亡、抗贫血和对急性肾损伤的保护作用。但人参皂苷Rk3是否能改善NASH尚未见报道。因此，本研究的目的是探讨人参皂苷Rk3对NASH的保护作用及其作用机制。C57BL/6小鼠建立NASH模型后给予不同剂量的人参皂苷Rk3治疗。我们的结果表明，Rk3 给药显着改善了由高脂肪高胆固醇 (HFHC) 饮食和 CCl 引起的肝脏炎症、脂质沉积和纤维化_4.小鼠注射。值得注意的是，人参皂苷 Rk3 可显着抑制 PI3K/AKT 信号通路。此外，人参皂苷 Rk3 处理显着改善了短链脂肪酸的丰度。这些变化与肠道微生物群的多样性和组成的有益变化有关。总之，人参皂苷 Rk3 可改善肝脏非酒精性脂质炎症并引发有益肠道菌群的变化，有助于揭示宿主与微生物的相互作用。这项研究的结果表明，人参皂苷 Rk3 是治疗 NASH 的有前途的候选药物。