中国比较医学杂志2025，Vol.35Issue(12)：13-30,18.DOI:10.3969/j.issn.1671-7856.2025.12.002
基于网络药理学和孟德尔随机化探究异鼠李素防治肝纤维化的分子机制
Exploring the molecular mechanism of isorhamnetin against liver fibrosis based on network pharmacology and Mendelian randomization
摘要
Abstract
Objective To investigate the core targets and mechanisms by which isorhamnetin prevents and ameliorates liver fibrosis.Methods Bioinformatic data were integrated to identify liver fibrosis-related targets via differential gene analysis and weighted gene co-expression network analysis(WGCNA).These targets were compared with those that mediate isorhamnetin's action to identify common targets.Machine learning optimized core targets that were validated for causal association using Mendelian randomization.Molecular docking and dynamics simulations assessed target function.Results We identified 113 interactive targets of liver fibrosis and isorhamnetin,which were primarily enriched in phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT),tumor necrosis factor(TNF),and other signaling pathways.Machine learning combined with Mendelian randomization pinpointed aryl hydrocarbon receptor(AHR),caspase3(CASP3),and mitogen-activated protein kinase 14(MAPK14)as core targets.Multi-dataset validation confirmed their consistent expression and significant diagnostic efficacy(area under the curve＞0.7).Molecular simulations demonstrated stable binding of isorhamnetin to these targets(binding energy＜-7.0 kcal/mol).Conclusions Isorhamnetin inhibits liver fibrosis by targeting AHR,CASP3,and MAPK14 to regulate inflammation,apoptosis,and metabolic pathways.This study provides novel insights into the anti-fibrotic mechanisms of traditional Chinese medicine components.关键词
异鼠李素/肝纤维化/网络药理学/孟德尔随机化/分子动力学模拟Key words
isorhamnetin/liver fibrosis/network pharmacology/Mendelian randomization/molecular dynamics simulation分类
医药卫生引用本文复制引用
郑洋,王佳慧,赵铁建,汪磊,梁亮,肖华业,杨仕权..基于网络药理学和孟德尔随机化探究异鼠李素防治肝纤维化的分子机制[J].中国比较医学杂志,2025,35(12):13-30,18.基金项目
国家自然科学基金(82204755) （82204755）
广西自然科学基金(2023GXNSFBA026274,2024GXNSFAA010235) （2023GXNSFBA026274,2024GXNSFAA010235）
广西壮瑶药重点实验室基金资助项目(GXZYYKF2023-05) （GXZYYKF2023-05）
广西研究生教育创新计划项目(YCBZ2024150) （YCBZ2024150）
广西中医药大学赛恩斯新医药学院科研项目(2024ZZA006,2024ZZA003,2024ZZB002,2024ZZB007,2024ZZB010) （2024ZZA006,2024ZZA003,2024ZZB002,2024ZZB007,2024ZZB010）
广西中医药大学赛恩斯新医药学院重点实验室(No.02:中医药壮瑶医药防治慢性肝病的基础研究). （No.02:中医药壮瑶医药防治慢性肝病的基础研究）
