AUTHOR=Qin Chufeng , Luo Lichuan , Cui Yusheng , Jiang Li , Li Beilei , Lou Yijie , Weng Zhuofan , Lou Jingwen , Liu Chenxin , Weng Cuiting , Wang Zhaojun , Ji Yunxi 

TITLE=Anti-Autophagy Mechanism of Zhi Gan Prescription Based on Network Pharmacology in Nonalcoholic Steatohepatitis Rats

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.708479

DOI=10.3389/fphar.2021.708479

ISSN=1663-9812

ABSTRACT=<p><bold>Background and Aims:</bold> Zhi Gan prescription (ZGP) has been clinically proven to exert a favorable therapeutic effect on nonalcoholic steatohepatitis (NASH). This study purpose to reveal the underlying molecular mechanisms of ZGP action in NASH.</p><p><bold>Methods:</bold> Systematic network pharmacology was used to identify bioactive components, potential targets, and the underlying mechanism of ZGP action in NASH. High fat (HF)-induced NASH model rats were used to assess the effect of ZGP against NASH, and to verify the possible molecular mechanisms as predicted by network pharmacology.</p><p><bold>Results:</bold> A total of 138 active components and 366 potential targets were acquired in ZGP. In addition, 823 targets of NASH were also screened. <italic>In vivo</italic> experiments showed that ZGP significantly improved the symptoms in HF-induced NASH rats. qRT-PCR and western blot analyses showed that ZGP could regulate the hub genes, PTEN, IL-6 and TNF in NASH model rats. In addition, ZGP suppressed mitochondrial autophagy through mitochondrial fusion and fission via the PINK/Parkin pathway.</p><p><bold>Conclusion:</bold> ZGP exerts its effects on NASH through mitochondrial autophagy. These findings provide novel insights into the mechanisms of ZGP in NASH.</p>