基于网络药理学研究三妙散治疗骨关节炎的药理机制

Elucidation of Mechanisms of Sanmiaosan in the Treatment of Osteoarthritis Based on Network Pharmacology

目的:基于网络药理学方法研究中医方剂三妙散治疗骨关节炎(osteoarthritis,OA)的药理机制,分析其作用的活性成分、关键靶点和信号通路,以期为三妙散治疗骨关节炎提供理论支持。方法和结果:通过中药系统药理学数据库与分析平台(TCMSP)和DrugBank数据库发现了三妙散的57个潜在活性成分和203个作用靶点,通过GeneCards、TTD、OMIM、DisGeNET和PharmGKB数据库得到1971个骨关节炎相关靶点,利用韦恩分析发现了108个与药物靶点的交集靶点,且交集靶点主要来自化合物槲皮素、山奈酚和汉黄芩素。对交集靶点进行蛋白质相互作用(PPI)分析,将结果导入Cytoscape软件利用CytoNCA插件进行拓扑分析,得到9个三妙散治疗骨关节炎的关键靶点。DAVID富集分析发现,三妙散治疗骨关节炎的主要生物学过程包括氧化应激、对活性氧的反应,凋亡信号通路等;信号通路主要包括PI3KAkt、IL17、TNF及细胞凋亡等。结论:三妙散的主要成分槲皮素、山奈酚和汉黄芩素等可能通过ESR1、FOS、JUN、MAPK1、MAPK14、RELA、TP53、TNF和MYC靶点,作用于PI3KAkt信号通路、IL17信号通路、TNF信号通路、细胞凋亡信号通路等而发挥治疗骨关节炎的作用。

Objective:Based on the therapeutic mechanism of Chinese medicine sanmiaosan(SMS)in the treatment of osteoarthritis(OA),to analyze the active ingredients and key targets,and investigate the acting pathways using network pharmacology approaches,so as to provide theoretical support for SMS treating OA.Methods and Results:57 active ingredients and 203 targets of SMS were identified by Traditional Chinese Medicine Systems Pharmacology(TCMSP)database and DrugBank database,and 1971 OA related targets were collected by GeneCards,Therapeutic Target Database(TTD),Online Mendelian Inheritance in Man(OMIM),DisGeNET,and Pharmaco-genetics Knowledge Base(PharmGKB)databases.After Venn analysis,108 common targets of SMS and OA were obtained,and they were mainly from quercetin,kaempferol and wogonin.The common targets were analyzed by protein-protein interaction(PPI),and then the results were imported into Cytoscape software for topological analysis using CytoNCA.Finally,9 key targets of SMS for the treatment of OA were obtained.According to DAVID enrichment analysis,the main biological processes of SMS in the treatment of OA include oxidative stress,response to reactive oxygen species and apoptotic signaling pathways,and the enriched signaling pathways mainly include PI3K-Akt,IL-17,TNF and apoptosis.Conclusion:The data suggested that the main ingredients of SMS,such as quercetin,kaempferol and wogonin,may play the role in the treatment of OA through the target of ESR1,FOS,JUN,MAPK1,MAPK14,RELA,TP53,TNF and MYC,and act on PI3K-Akt,IL-17,TNF and apoptosis signaling pathways.