山西医科大学学报2026，Vol.57Issue(8)：875-884,10.DOI:10.13753/j.issn.1007-6611.2026.08.004
基于网络药理学与分子动力学模拟探究Moldavoside改善心肌纤维化的机制
Mechanism of Moldavoside alleviating myocardial fibrosis based on network pharmacology and molecular dynamics simulation
摘要
Abstract
Objective To explore the therapeutic targets and molecular mechanisms of Moldavoside,an active ingredient of the traditional Uyghur herbal medicine Badi Ranjibuya,in ameliorating myocardial fibrosis.Methods Network pharmacology was employed to screen intersecting targets between Moldavoside and myocardial fibrosis.A protein-protein interaction network was constructed,and the proteins were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Molecular docking and molecular dynamics simulations were performed to evaluate the binding affinity between Moldavoside and the identified key targets.The mice were randomized into control group,angiotensin Ⅱ(Ang Ⅱ)group,and Ang Ⅱ+Moldavoside(daily intragastric administration of Moldavoside at 15 mg/kg for 28 consecutive days)group.Myocardial fibrosis area was assessed by Sirius red staining.The phosphorylation level of JAK1 at Tyr1034/Tyr1035 in myocardial tissues was determined by Western blot.Chromatin immunopre-cipitation(ChIP)assay was performed to verify the transcriptional regulation of RhoE by STAT3.Results A total of 60 intersecting targets of Moldavoside against myocardial fibrosis were identified.Enrichment analyses result indicated that the JAK1/STAT3 pathway was the core signaling pathway mediating the anti-fibrotic effect of Moldavoside.Molecular dynamics simulation results confirmed that Moldavoside could stably bind to the JAK1 protein.Sirius red staining result revealed that the fibrotic area fraction in Ang Ⅱ group was significantly higher than that in control group(5.013±0.517 vs 1.021±0.156,P<0.05),whereas it was significantly lower in Ang Ⅱ+Moldavoside group than in Ang Ⅱ group(1.060±0.189 vs 5.013±0.515,P<0.05).Western blot results demonstrated that the relative protein expression level of phosphorylated JAK1(Tyr1034/Tyr1035)in myocardial tissues was significantly lower in Ang Ⅱ+Moldavo-side group than in Ang Ⅱ group(0.412±0.076 vs 1.000±0.099,P<0.05).The ChIP assay result confirmed that STAT3 was a direct transcription regulator of RhoE.Conclusion Moldavoside can attenuate myocardial fibrosis by suppressing the activation of JAK1/STAT3-RhoE pathway,suggesting that it can be a novel candidate agent for the targeted therapy of myocardial fibrosis.关键词
Moldavoside/RhoE/心脏重塑/网络药理学/分子动力学模拟/JAK1/STAT3Key words
Moldavoside/RhoE/cardiac remodeling/network pharmacology/molecular dynamics simulation/JAK1/STAT3分类
医药卫生引用本文复制引用
张碧雪,孙源良,王婷婷,程征,周心涛..基于网络药理学与分子动力学模拟探究Moldavoside改善心肌纤维化的机制[J].山西医科大学学报,2026,57(8):875-884,10.基金项目
国家自然科学基金面上项目(82070282) （82070282）
国家自然科学基金青年项目(82200404) （82200404）
中国博士后基金面上项目(2022MD723777) （2022MD723777）
黑龙江省博士后基金面上项目(LBH-Z22216) （LBH-Z22216）
陕西省重点研发项目(2023-YBSF-346) （2023-YBSF-346）
新疆维吾尔自治区"天池英才"人才项目:青年博士人才 （）
