Zhizi-Bopi decoction ameliorates ANIT-induced cholestatic liver injury in mice through IL-17/NF-κB inflammatory pathwaysOA
Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.
Wei Cui;Tian Chen;Jie-Yao Huang;Xiao-Fei Bi;Wen-Jin Zhang;Yan-Jun Hu;Li-Juan Deng;Wei Fang;Chang-Hui Liu;Ya-Ping Xiao
Department of Pharmacy,Chongqing University Three Gorges Hospital,Chongqing 404000,China School of Medicine,Chongqing University,Chongqing 400030,ChinaSchool of Medicine,Chongqing University,Chongqing 400030,China Health Management Center,Chongqing University Three Gorges Hospital,Chongqing 404000,ChinaDepartment of Pharmacy,Chongqing University Three Gorges Hospital,Chongqing 404000,China School of Medicine,Chongqing University,Chongqing 400030,ChinaSchool of Medicine,Chongqing University,Chongqing 400030,China Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases,Chongqing University Three Gorges Hospital,Chongqing 404000,ChinaSchool of Medicine,Chongqing University,Chongqing 400030,China Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases,Chongqing University Three Gorges Hospital,Chongqing 404000,ChinaDepartment of Pharmacy,Chongqing University Three Gorges Hospital,Chongqing 404000,China School of Medicine,Chongqing University,Chongqing 400030,ChinaDepartment of Pharmacy,Chongqing University Three Gorges Hospital,Chongqing 404000,China School of Medicine,Chongqing University,Chongqing 400030,ChinaDepartment of Pharmacy,Chongqing University Three Gorges Hospital,Chongqing 404000,China School of Medicine,Chongqing University,Chongqing 400030,ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome,School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510405,ChinaDepartment of Pharmacy,Chongqing University Three Gorges Hospital,Chongqing 404000,China School of Medicine,Chongqing University,Chongqing 400030,China
医药卫生
Zhizi-Bopi decoctioncholestatic liver injurynetwork pharmacologysingle-cell RNA sequencingIL-17/NF-κB signaling pathway
《Traditional Medicine Research》 2026 (1)
P.47-59,13
supported by the National Science Foundation of China(No.82405004,82474253)the Natural Science Foundation postdoctoral project of Chongqing(CSTB2022NSCQ-BHX0709)Chongqing Wanzhou District doctoral“through train”scientific research project(wzstc-20220124)Natural Science Foundation of Chongqing,China(No.Cstc2021jcyj-msxmX0996)Chongqing Wanzhou District Science and Health Joint Medical Research Project(wzstc-kw2023032)。
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