Deciphering the mechanism of action of Chaihu-Astragalus compound in the management of alcoholic liver fibrosis:A network pharmacology and molecular docking approach  

基于网络药理学及分子对接技术探讨柴胡-黄芪治疗酒精性肝纤维化的作用机制

作　　者：Xiaodong Zhu Xueshi Di Jinhui Sun 朱晓东;邸学士;孙劲晖(广西中医药大学,广西南宁530299;北京中医药大学,北京100029;北京中医药大学东直门医院,北京100700)

机构地区：[1]Guangxi University of Chinese Medicine,Nanning 530299,Guangxi,China [2]Beijing University of Chinese Medicine,Beijing 100029,China [3]Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2025年第2期163-174,共12页中国药学(英文版)

基　　金：National Natural Science Foundation of China(Grant No.81573969).

摘　　要：The present study aimed to analyze the potential mechanism of action of Chaihu-Astragalus in treating alcoholic liver fibrosis using network pharmacology and molecular docking techniques.We initially screened the active ingredients and targets of Chaihu-Astragalus through the TCMSP database.Additionally,we identified disease-related targets associated with alcoholic liver fibrosis via the GeneCards database,subsequently obtaining the intersection targets of Chaihu-Astragalus for treating alcoholic liver fibrosis.Using Cytoscape software,we constructed a“drug-active ingredient-intersection target”network and evaluated the network’s major active ingredients.The intersection targets were then subjected to protein-protein interaction network analysis using the STRING database to identify possible core targets.GO functional and KEGG pathway enrichment analyses were conducted using the DAVID platform.Molecular docking verification of key active ingredients and core targets was performed using Schrödinger software and the Maestro platform.We identified 26 active ingredients and 180 potential targets(intersection targets).Key active compounds,such as quercetin,kaempferol,prickly mangosteen,isorhamnetin,and Areapillin,were highlighted.Core targets were also identified,including AKT1,TP53,JUN,TNF,and IL-6.Enrichment analyses revealed that potential targets were mainly associated with PI3K-Akt,TNF,MAPK,and other signaling pathways.Chaihu-Astragalus acted on multiple targets such as AKT1,TP53,and JUN primarily through various active ingredients like quercetin and kaempferol.Thus,it affected treating alcoholic liver fibrosis through multiple signaling pathways,such as PI3K-Akt,TNF,and MAPK.It demonstrated characteristics of being multi-component,multi-target,and multi-pathway in its approach.本研究旨在通过网络药理学和分子对接技术分析柴胡-黄芪治酒精性肝纤维化的潜在作用机制。通过TCMSP数据库筛选柴胡-黄芪的活性成分及作用靶点,通过GeneCards数据库筛选酒精性肝纤维化的疾病相关靶点,获取二者交集靶点,即柴胡-黄芪治疗酒精性肝纤维化的潜在作用靶点。使用Cytoscape软件构建“中药-活性成分-交集靶点”网络,并分析网络中的关键活性成分;利用STRING数据库对交集靶点进行蛋白互作(PPI)网络分析,筛选出潜在核心靶点;运用DAVID平台对交集靶点进行GO功能和KEGG通路富集分析;利用Schrödinger软件、Maestro平台对关键活性成分与关键靶点进行分子对接验证。结果共筛选得到26个活性成分及180个潜在作用靶点(交集靶点);获得槲皮素、山奈酚、刺芒柄花素、异鼠李素、茵陈黄酮等关键活性化合物;筛选得到AKT1、TP53、JUN、TNF、IL6等核心靶点;潜在作用靶点主要富集在PI3K-Ak、TNF、MAPK等信号通路。研究表明,柴胡-黄芪主要通过槲皮素、山柰酚等多种活性成分,作用于AKT1、TP53、JUN等多靶点,通过PI3K-AKT、TNF、MAPK等多条信号通路来发挥治疗酒精性肝纤维化的作用,具有多成分、多靶点、多通路的特点。

关 键 词：Alcoholic liver fibrosis Chaihu-Astragalus Network pharmacology Molecular docking 

分 类 号：R284[医药卫生—中药学]