中国中医骨伤科杂志2026，Vol.34Issue(1)：67-77,11.DOI:10.20085/j.cnki.issn1005-0205.260110
网络药理学联合分子动力学探索地黄饮子治疗膝骨关节炎的疗效分析及实验验证
Application of Network Pharmacology Combined with Molecular Dynamics to Explore the Therapeutic Efficacy of Dihuang Yinzi Decoction in Treating Knee Osteoarthritis and Experimental Verification
摘要
Abstract
Objective:To reveal the core active components,key targets,and mechanism of action of Dihuang Yinzi decoc-tion in treatment of knee osteoarthritis(KOA)by using network pharmacology combined with molecular dynamics simulation(MDS)and cell experiments.Methods:The active components and targets of Dihuang Yinzi decoction were screened using the TCMSP and BATMAN-TCM databases,and the disease targets of KOA were obtained from the Gen-eCards and other databases.A"Chinese medicine-active com-ponent-interaction targets-disease"network was constructed and GO/KEGG enrichment analysis was performed.Molecu-lar docking and MDS were conducted using AutoDock Vina and GROMACS software to verify the binding stability between core components and targets.The chondroprotective effect of Dihuang Yinzi decoction and core components was verified through IL-1β-induced chondrocyte inflammation mod-els using CCK-8,Alcian blue staining,immunofluorescence,qPCR,and Western Blot methods.Results:123 active compo-nents of Dihuang Yinzi decoction were screened out,corresponding to 483 targets.The intersection with KO A disease tar-gets yielded 77 key targets(including IL-6,AKT1,CASP3,HIF-1α,etc.).GO/KEGG enrichment analysis showed that it mainly regulated TNF signaling pathway,the HIF-1α signaling pathway,PI3K-Akt signaling pathway,etc.,involving bio-logical processes such as inflammation regulation,cell apoptosis and cartilage matrix metabolism.Molecular docking and dynamics simulations confirmed that echinacoside stably binding binds to the core targets of KO A,HIF-1α and CASP3,with average binding free energy was-153.595 kJ/mol and-147.57 kJ/mol,respectively,and the complex conforma-tion was stable.Cell experiments showed that Dihuang Yinzi decoction(4 μg/mL)and echinacoside(16 μmol/L)could significantly up-regulate COL2A1 expression,down-regulate HIF-1α,CASP3,and MMP13 expression,protect the integri-ty of chondrocyte matrix,and inhibit inflammation and apoptosis.Conclusion:Dihuang Yinzi decoction treats KOA through the"multi-component-multi-target-multi-pathway"synergistic effect.The core component echinacoside can exert chondroprotective effects by inhibiting HIF-1α-mediated inflammatory cascade reactions and CASP3-dependent chondro-cyte apoptosis,providing theoretical support for the clinical treatment of KOA with Dihuang Yinzi decoction.关键词
地黄饮子/膝骨关节炎/网络药理学/软骨保护/炎症调控Key words
Dihuang Yinzi decoction/knee osteoarthritis/network pharmacology/chondroprotection/inflammation regulation分类
医药卫生引用本文复制引用
刘钊,杨杰,杜文喜..网络药理学联合分子动力学探索地黄饮子治疗膝骨关节炎的疗效分析及实验验证[J].中国中医骨伤科杂志,2026,34(1):67-77,11.基金项目
国家中医药综合改革示范区中医药科技共建项目(GZY-KJS-ZJ-2026-113)浙江中医药大学附属第一医院2022年附属医院科研专项资助项目(2022FSYYZQ08)浙江省中医药科技计划项目(2026ZL0330)浙江省卫生高层次人才创新人才项目(202148) （GZY-KJS-ZJ-2026-113）
