摘要
目的:运用网络药理学和分子对接技术探讨六味地黄丸合四妙丸治疗股骨头坏死的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)筛选出六味地黄丸合四妙丸的活性成分;利用UniProt数据库预测活性成分作用靶点,通过GeneCards和OMIM数据库预测股骨头坏死疾病靶点。通过STRING数据库构建潜在作用靶点和蛋白质-蛋白质相互作用网络并通过Cytoscape 3.10.1软件筛选出关键靶点。通过DAVID工具进行潜在靶点的基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。结果:六味地黄丸合四妙丸治疗股骨头坏死的有效成分主要为槲皮素、汉黄芩素、山柰酚;作用的核心靶点为白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、IL-1B、肿瘤蛋白p53(Tumor Protein p53,TP53)、含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase-3,CASP3)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、雌激素受体1(Estrogen Receptor 1,ESR1)、基质金属蛋白酶(Matrix Metallopeptidase,MMP)9、缺氧诱导因子-1A(Hypoxia Inducible Factor-1A,HIF-1A)、过氧化物酶体增殖物激活受体重组蛋白(Peroxisome Proliferator Activated Receptor,PPAR)γ等。关键作用通路为晚期糖基化终末产物-受体(Advanced Glycation End-Products,AGE-RAGE)信号通路、IL-17信号通路、脂质与动脉粥样硬化通路、癌症信号通路等。分子对接显示核心成分与核心靶点有较好的结合活性。结论:本研究初步揭示了六味地黄丸合四妙丸的核心活性成分及其多成分、多靶点、多通路治疗股骨头坏死的作用机制,为临床上股骨头坏死保髋治疗提供用药思路和依据。
Objective:To explore the mechanism of Liuwei Dihuang Wan(六味地黄丸)with the Simiao Wan(四妙丸)in the treatment of osteonecrosis of the femoral head(ONFH)by using network pharmacology and molecular docking.Methods:Active ingredients of Liuwei Dihuang Wan with Simiao Wan were screened from the TCMSP database.Target proteins of the active ingredients were predicted by using the UniProt database,and ONFH disease targets were predicted by using GeneCards and OMIM databases.A potential target-protein interaction(PPI)network was constructed using the STRING database,and key targets were selected by using Cytoscape 3.10.1 software.Enrichment analysis of potential targets was performed by using the DAVID tool for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG).Results:The effective components of Liuwei Dihuang Wan with Simiao Wan for treating ONFH were mainly quercetin,baicalein,and kaempferol.The core targets included interleukin-6(IL-6),tumor necrosis factor(TNF),interleukin-1B(IL-1B),tumor protein 53(TP53),caspase-3(CASP3),epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),matrix metalloproteinase 9(MMP9),hypoxia-inducible factor 1-alpha(HIF-1A),peroxisome proliferator-activated receptor(PPAR)γ,etc..Key pathways involved the AGE-RAGE signaling pathway,IL-17 signaling pathway,lipid and atherosclerosis pathway,and pathways in cancer.Molecular docking demonstrated good binding activity between core components and key targets.Conclusion:This study preliminarily reveals the core active components and the multi-component,multi-target,and multi-pathway mechanisms of Liuwei Dihuang Wan with Simiao Wan in treating ONFH,providing insights and a basis for clinical hip-preserving treatment of ONFH.
出处
《中医临床研究》
2024年第25期72-79,共8页
Clinical Journal Of Chinese Medicine
关键词
六味地黄丸
四妙丸
股骨头坏死
网络药理学
分子对接
Liuwei Dihuang Wan
Simiao Wan
Osteonecrosis of the femoral head
Network pharmacology
Molecular docking
