文献类型：期刊文献

英文题名：Multi-omics analysis elucidates the therapeutic mechanisms of the Quzhi formula in metabolic dysfunction-associated steatohepatitis targeting gut microbiota, lipid metabolism, and the role of its metabolite fraxin

作者：Wu, Jiao-Xiang[1,2,3,4];Wu, Yue-Lan[1,2,3,4];Li, Mei-Fang[5];Liu, Nian[6];Liu, Ying[7];Huang, Yan-Ping[1,2,3,4];Gan, Yuan[1,2,3,4];Wang, Xiao-Yu[1,2,3,4];Chai, Hai-Sheng[8];Xu, Jin[1,2,3,4];Xi, Qian[9];Guo, Xi-Rong[1,2,3,4];Sheng, Hui-Ming[1,2,3,4];Shen, Ting-Ting[1,2,3,4];Zhang, Qin[1,2,3,4]

第一作者：Wu, Jiao-Xiang

通信作者：Shen, TT[1];Zhang, Q[1];Shen, TT[2];Zhang, Q[2];Shen, TT[3];Zhang, Q[3];Shen, TT[4];Zhang, Q[4]

机构：[1]Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Phase Clin Trial Unit 1, Shanghai, Peoples R China;[2]Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Infect Dis, Shanghai, Peoples R China;[3]Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Clin Lab, Shanghai, Peoples R China;[4]Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Plast Surg Dept, Shanghai, Peoples R China;[5]Henan Univ, Zhengzhou, Peoples R China;[6]Shanghai Univ Sport, Ehlth Program Shanghai Antidoping Lab, Shanghai, Peoples R China;[7]Gansu Univ Chinese Med, Clin Coll Tradit Chinese Med, Lanzhou, Peoples R China;[8]Shanghai Univ Tradit Chinese Med, Yueyang Integrated Chinese & Western Med Hosp, Shanghai, Peoples R China;[9]Shanghai Pudong New Area Gongli Hosp, Dept Endocrinol, Shanghai, Peoples R China

第一机构：Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Phase Clin Trial Unit 1, Shanghai, Peoples R China

通信机构：[1]corresponding author), Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Phase Clin Trial Unit 1, Shanghai, Peoples R China;[2]corresponding author), Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Infect Dis, Shanghai, Peoples R China;[3]corresponding author), Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Clin Lab, Shanghai, Peoples R China;[4]corresponding author), Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Plast Surg Dept, Shanghai, Peoples R China.

年份：2025

卷号：16

外文期刊名：FRONTIERS IN PHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-105022120508);WOS:【SCI-EXPANDED(收录号:WOS:001615214200001)】；

基金：The author(s) declare that financial support was received for the research and/or publication of this article. This research was supported by National Natural Science Foundation of China (82300971), the Fundamental Research Funds for the Central Universities (YG2022QN116), the National Key Research and Development Program of China (2021YFC2701900, 2021YFC2701903), the Research Fund of Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine (TRKYRC-xx202212, TRYJ2022LC03, TR2014rc03), the Research Fund of Health Commission of Jing'an District (2024QT02).

语种：英文

外文关键词：metabolic dysfunction-associated steatohepatitis (MASH); Quzhi formula (QZF); fraxin; AMPK; autophagy

摘要：Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced stage of fatty liver disease with no approved pharmacotherapies. The Quzhi Formula (QZF), a traditional Chinese medicine utilized clinically for nearly two decades, has shown promising efficacy against MASH; however, its mechanisms of action remain largely unexplored. To elucidate these mechanisms, we conducted a multi-omics investigation integrating 16S rRNA sequencing, untargeted metabolomics, and transcriptomics in a MASH mouse model, with findings validated by histology. QZF treatment significantly alleviated hepatic steatosis, restored gut microbial diversity, and suppressed the proliferation of Enterococcus, a genus implicated in MASH pathogenesis. Transcriptomic and metabolomic analyses demonstrated that QZF's therapeutic effects were mediated through the regulation of lipid metabolic pathways and the activation of autophagy. Furthermore, we identified fraxin as a pivotal bioactive metabolite contributing to QZF-induced autophagy. Our study demonstrates that QZF ameliorates MASH in a concerted manner by remodeling the gut microbiota, reprogramming hepatic metabolism, and promoting autophagy via fraxin. These results provide a comprehensive mechanistic foundation for QZF as a multi-targeted therapeutic candidate for MASH.