Integration of network pharmacology and serum medicinal chemistry to investigate the pharmacological mechanisms of QiZhuYangGan Decoction in the treatment of hepatic fibrosis

作者全名："Deng, Jing-Wei; Yuan, Su; Shi, Li-Peng; Chen, Xin; Liu, Jun; Chen, Zhi-Wei; Tan, Kai-Yue; Yang, Qian; Cao, Wen-Fu"

作者地址："[Yuan, Su; Shi, Li-Peng; Chen, Xin; Liu, Jun; Tan, Kai-Yue; Yang, Qian; Cao, Wen-Fu] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing, Peoples R China; [Deng, Jing-Wei; Yuan, Su; Shi, Li-Peng; Chen, Xin; Liu, Jun; Chen, Zhi-Wei; Tan, Kai-Yue; Yang, Qian; Cao, Wen-Fu] Chongqing Key Lab Tradit Chinese Med Prevent & Cu, Chongqing, Peoples R China; [Yuan, Su; Liu, Jun; Cao, Wen-Fu] Chongqing Med Univ, Affiliated Hosp 1, Dept Combinat Chinese & Western Med, Chongqing, Peoples R China; [Cao, Wen-Fu] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Cao, WF (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF ETHNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001163955900001

JCR分区：Q1

影响因子：5.4

年份：2024

卷号：323

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Hepatic fibrosis; Network pharmacology; Traditional Chinese medicine; Molecular docking; Molecular dynamics simulation

摘要："Ethnopharmacological relevance: Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific target and mechanism of action of QZD for hepatic fibrosis treatment remain unknown. Aim of the study: By combining network pharmacology, serum medicinal chemistry, and experimental validation methods, our study aimed to investigate the therapeutic effects of QZD on hepatic fibrosis, the anti-hepatic fibrosis active ingredients, and the possible mechanism of anti-hepatic fibrosis action. Materials and methods: The study aimed to investigate the therapeutic effect of QZD on hepatic fibrosis induced by CCl4 in SD rats, as well as its mechanism of action. The rats were anesthetized intraperitoneally using 3% pentobarbital and were executed after asphyxiation with high concentrations of carbon dioxide. Several techniques were employed to evaluate the efficacy of QZD, including ELISA, Western blot, HYP reagent assay, and various pathological examinations such as HE, Masson, Sirius Red staining, and immunohistochemistry (IHC). Additionally, serum biochemical assays were conducted to assess the effect of QZD on liver injury. Network pharmacology, UPLC, molecular docking, and molecular dynamics simulation were utilized to explore the mechanism of QZD in treating hepatic fibrosis. Finally, experimental validation was performed through ELISA, IHC, RT-qPCR, and Western blot analysis. Result: Liver histopathology showed that QZD reduced inflammation and inhibited collagen production, and QZD significantly reduced HA and LN content to treat hepatic fibrosis. Serum biochemical analysis showed that QZD improved liver injury. Network pharmacology combined with UPLC screened six active ingredients and obtained 87 targets for the intersection of active ingredients and diseases. The enrichment analysis results indicated that the PI3K/AKT pathway might be the mechanism of action of QZD in the treatment of hepatic fibrosis, and counteracting the inflammatory response might be one of the pathways of action of QZD. Molecular docking and molecular dynamics simulations showed that the active ingredient had good binding properties with PI3K, AKT, and mTOR proteins. Western blot, ELISA, PCR, and IHC results indicated that QZD may treat hepatic fibrosis by inhibiting the PI3K/AKT/mTOR pathway and suppressing M1 macrophage polarization, while also promoting M2 macrophage polarization. Conclusions: QZD may be effective in the treatment of hepatic fibrosis by inhibiting the PI3K/AKT/mTOR signaling pathway and M1 macrophage polarization, while promoting M2 macrophage polarization. This provides a strong basis for the clinical application of QZD."

基金机构："National Natural Science Foundation of China [81573860, 82004168]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202215101, KJZD-K202315101]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No. 81573860, No. 82004168) , Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No.: KJQN202215101, KJZD-K202315101) . We thank the au- thors for the development of the database and software used in this paper, we also thank Figdraw ( www.figdraw.com ) for the assistance in creating flow chart."