Gynostemma Pentaphyllum ameliorates CCl-induced liver injury via PDK1/Bcl-2 pathway with comprehensive analysis of network pharmacology and transcriptomics.
Linlan Hu: College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
Xin Zhao: College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
Xian He: School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.
Yafei Guo: School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.
Hanxiao Cheng: School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.
Shaoting Chen: School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China.
Guangde Zhou: Centre for Clinical Pathology, Beijing You'an Hospital, Capital Medical University, No.8 Outside You'anmen, Fengtai District, Beijing, 100069, China. guangdez@sina.com.
Jiabo Wang: College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China. jiabo_wang@ccmu.edu.cn.
Yawen Lu: School of Traditional Chinese Medicine, Capital Medical University, No.10 Outside You'anmen, Fengtai District, Beijing, 100069, China. ywlu0411@163.com. ORCID
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 (CCl)-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 CCl-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.
