Yan Di, Zhang Xiaoling, Ma Chengmei, Huang Wenting, Hao Mimi, Xie Lan
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Medical Systems Biology Research Center, School of Medicine, Tsinghua University, Beijing 100084, China.
Pharmaceuticals (Basel). 2024 Aug 27;17(9):1128. doi: 10.3390/ph17091128.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD. The livers of patients with NASH are more likely to develop fibrosis. Xiaoyao San (XYS) is a classic traditional Chinese medicine (TCM) formula that has been widely used in treating liver diseases. In this study, we elucidated the effects and mechanism of XYS in treating NASH-related liver fibrosis by combining high-throughput sequencing-based high-throughput screening with network pharmacology analysis. Our work revealed that XYS may play a role in preventing NASH-related liver fibrosis by regulating biological functions related to the extracellular matrix (ECM), inflammation, and metabolism. Additionally, , , , and are the key herbs of XYS that could partially represent the functions of XYS. These regulatory effects are mediated by targeting signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NFκB), and peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Narcissin, casuarictin, and γ-sitosterol were identified as representative active compounds in XYS targeting STAT3, NFκB, and PPARγ, respectively. Taken together, our findings provide a novel strategy for investigating the pharmacological effects and biological mechanisms of a TCM formula.
非酒精性脂肪性肝病（NAFLD）是全球肝病的主要原因。非酒精性脂肪性肝炎（NASH）是NAFLD的一种晚期形式。NASH患者的肝脏更易发生纤维化。逍遥散（XYS）是一种经典的中药配方，已广泛用于治疗肝病。在本研究中，我们通过基于高通量测序的高通量筛选与网络药理学分析相结合，阐明了逍遥散治疗NASH相关肝纤维化的作用及机制。我们的研究表明，逍遥散可能通过调节与细胞外基质（ECM）、炎症和代谢相关的生物学功能，在预防NASH相关肝纤维化中发挥作用。此外， 、 、 及 是逍遥散的关键药材，它们可部分代表逍遥散的功效。这些调节作用是通过靶向信号转导和转录激活因子3（STAT3）、核因子κB（NFκB）和过氧化物酶体增殖物激活受体γ（PPARγ）信号通路介导的。分别鉴定出水仙苷、桤木酮和γ-谷甾醇为逍遥散中靶向STAT3、NFκB和PPARγ的代表性活性成分。综上所述，我们的研究结果为研究中药配方的药理作用和生物学机制提供了一种新策略。
