背景:绞股蓝(Thunb。)牧野,俗称“南方人参”,含有大量的人参皂苷衍生物,并表现出与人参相似的生物活性(C.A.MEY)(人参),通常用作人参的低成本替代品。绞股蓝对肝脏疾病有治疗作用。然而,其肝脏保护作用的潜在机制尚未完全阐明。
方法:使用实验性四氯化碳(CCl4)诱导的肝病模型评估了绞股蓝乙醇提取物(GPE)的保护作用。使用“药物-疾病”生物信息学分析预测GPE的潜在靶标。此外,全面的网络药理学和转录组学方法被用来研究GPE在肝病治疗中的潜在机制。
结果:病理检查显示,GPE可明显减轻肝细胞坏死和肝损伤。在CCl4诱导的肝细胞凋亡过程中,GPE显着下调Bax和切割PARP的表达,并上调Bcl-2的表达。我们比较了GPE中四种典型化合物的作用-GPE和人参共享的人参皂苷(Rb3)和GPE中三种独特的绞股蓝皂苷。值得注意的是,绞股蓝皂甙A(GPA),GPE中一种独特的皂苷,肝细胞凋亡显著减少。相比之下,人参皂苷Rb3的作用较弱。网络药理学和转录组学分析表明,这种抗凋亡作用是通过上调PDK1介导的PI3K/Akt信号通路来实现的。
结论:这些结果表明,绞股蓝具有良好的保肝作用,其机制主要涉及GPA上调PDK1/Bcl-2信号通路,从而防止细胞凋亡。
BACKGROUND: Gynostemma pentaphyllum (Thunb.) Makino, commonly known as \"southern ginseng\", contains high amounts of ginsenoside derivatives and exhibits similar biological activities with Panax ginseng (C. A. MEY) (ginseng), which is usually used as a low-cost alternative to ginseng. G. pentaphyllum has therapeutic effects on liver diseases. However, the mechanisms underlying its hepatoprotective action have not been fully elucidated.
METHODS: The protective effects of the ethanolic extract of G. pentaphyllum (GPE) were evaluated using an experimental carbon tetrachloride (CCl4)-induced liver disease model. Potential targets of GPE were predicted using the \"Drug-Disease\" bioinformatic analysis. Furthermore, comprehensive network pharmacology and transcriptomic approaches were employed to investigate the underlying mechanisms of GPE in the treatment of liver disease.
RESULTS: The pathological examinations showed that GPE significantly alleviated hepatocyte necrosis and liver injury. GPE significantly downregulated Bax and cleaved-PARP expression and upregulated Bcl-2 expression during CCl4-induced hepatocyte apoptosis. We compared the effects of four typical compounds in GPE -a ginsenoside (Rb3) shared by both GPE and ginseng and three unique gypenosides in GPE. Notably, Gypenoside A (GPA), a unique saponin in GPE, markedly reduced hepatocyte apoptosis. In contrast, ginsenoside Rb3 had a weaker effect. Network pharmacology and transcriptomic analyses suggested that this anti-apoptotic effect was achieved by upregulating the PI3K/Akt signaling pathway mediated by PDK1.
CONCLUSIONS: These results suggested that G. pentaphyllum had a promising hepatoprotective effect, with its mechanism primarily involving the upregulation of the PDK1/Bcl-2 signaling pathway by GPA, thereby preventing cell apoptosis.