Gynostemma Pentaphyllum Ameliorates CCl-induced Liver Injury Via PDK1/Bcl-2 Pathway with Comprehensive Analysis of Network Pharmacology and Transcriptomics

Overview

Journal Chin Med

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2024 May 15

PMID 38750545

Authors

Linlan Hu

Xin Zhao

Xian He

Yafei Guo

Hanxiao Cheng

Shaoting Chen

Guangde Zhou

Jiabo Wang

Yawen Lu

Affiliations

Soon will be listed here.

Abstract

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.

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