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This study aimed to explore the mechanism of <jats:italic>Hovenia<\/jats:italic> genus in the treatment of hepatic fibrosis by an integrative strategy combining network pharmacology analysis, molecular docking, transcriptomics and experimental validation. The traditional Chinese medicine systems pharmacology (TCMSP) database and literatures were used to collect the components of <jats:italic>Hovenia<\/jats:italic> genus. Public databases including GeneCards, TTD, PharmGkb were used to acquire the putative targets. The GO and KEGG analysis were applied to explore the underlying mechanisms. Furthermore, The TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 induced hepatic stellate cells (HSCs) model were performed to evaluate the anti\u2010hepatic fibrosis activity of <jats:italic>Hovenia<\/jats:italic> genus. The RT\u2010qPCR, Western blotting and flow cytometry experiments were used to validate the anti\u2010hepatic fibrosis mechanisms of Hovenianin A. The KEGG analysis of network pharmacology and transcriptomics revealed that the core targets mainly enriched in PI3K\u2010Akt signaling pathways. The cell screening results indicated flavonoids were the main active ingredients of <jats:italic>Hovenia<\/jats:italic>. Hovenianin A, a bioactive bisflavonol, was validated to promote the apoptosis of HSCs by inhibiting PI3K\u2010Akt pathway. Molecular docking further corroborated the binding sites between Hovenianin A and AKT1. In summary, <jats:italic>Hovenia<\/jats:italic> may have therapeutic effects on liver fibrosis by modulating the PI3K\u2010Akt apoptosis pathway. Our findings may facilitate the development of <jats:italic>Hovenia<\/jats:italic> genus, which could help to treat liver fibrosis in the future.<\/jats:p>","DOI":"10.1002\/cbdv.202201110","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T10:54:20Z","timestamp":1677236060000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hovenianin A Alleviates Hepatic Fibrosis by Inhibiting the PI3K\/AKT Pathway in TGF\u2010\u03b21\u2010Induced HSCs Based on Network Pharmacology and Transcriptomic Analysis"],"prefix":"10.1002","volume":"20","author":[{"given":"Xiaolan","family":"Kuang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine The Second Clinical College of Guangzhou University of Chinese Medicine  Guangzhou &lt;510006&gt; China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Ma","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine The Second Clinical College of Guangzhou University of Chinese Medicine  Guangzhou &lt;510006&gt; China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanna","family":"Cai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine The Second Clinical College of Guangzhou University of Chinese Medicine  Guangzhou &lt;510006&gt; China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhan","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine The Second Clinical College of Guangzhou University of Chinese Medicine  Guangzhou &lt;510006&gt; China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Engineering Research Center for Modernization of TCM NMPA Key Laboratory for Quality Evaluation of TCM Jinan University  Guangzhou 510632 P. 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