基于网络药理学和分子对接探讨蠲痹汤治疗骨关节炎的机制

Mechanism of Juanbi decoction for osteoarthritis based on network pharmacology and molecular docking

目的采用网络药理学和分子对接探讨蠲痹汤治疗骨关节炎的机制。方法应用TCMSP数据库获取蠲痹汤的活性成分和对应靶点,检索GeneCards数据库、OMIM数据库、PharmGkb数据库和TTD数据库获得骨关节炎的治疗靶点。运用R语言软件(版本4.0.2)获得蠲痹汤治疗骨关节炎的交集靶点,使用Cytoscape软件(版本3.8.0)构建“活性成分—治疗靶点”网络并将关键成分进行排序,同时通过蛋白质相互作用(PPI)网络筛选出其核心靶点。运用R语言软件对蠲痹汤治疗骨关节炎的作用靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析。运用AutoDockVina(版本1.1.2)等软件对上述核心靶点及关键成分进行分子对接验证。结果应用TCMSP数据库共得到蠲痹汤活性成分165个及对应靶点2529个,药物药效靶点与骨关节炎治疗靶点取交集得到115个靶点,关键成分有槲皮素、山柰酚、柚皮素等,核心靶点有STAT3、TNF、MAPK14等。GO富集分析得到2306个生物过程条目,144个分子功能条目,69个细胞组成条目;KEGG富集分析得到TNF信号通路、IL-17信号通路、PI3K-AKT信号通路等相关通路。分子对接结果显示,蠲痹汤治疗骨关节炎的关键成分槲皮素、山柰酚、柚皮素、甘草酮A、刺芒柄花素与其对应的核心靶点有较好的结合性。结论蠲痹汤可能通过多成分、多靶点、多通路的相互作用发挥对骨关节炎的治疗作用。

Objective To explore the mechanism of Juanbi decoction in the treatment of osteoarthritis by network pharmacology and molecular docking.Methods The active ingredients and corresponding targets of Juanbi decoction were obtained from TCMSP database,and the therapeutic targets of osteoarthritis were obtained by searching GeneCards database,OMIM database,PharmGkb database and TTD database.The intersection targets of Juanbi decoction in the treatment of osteoarthritis were obtained from R language software(version 4.0.2).The Cytoscape software(version 3.8.0)was used to construct the network of‘active ingredient-therapeutic target',and ranked the key ingredients,meanwhile,the protein-protein interaction(PPI)network was used to screen the core targets.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis on the active targets of Juanbi decoction in the treatment of osteoarthritis were performed by using R language software.AutoDockVina(version 1.1.2)and other software were used to verify the molecular docking of the above core targets and key ingredients.Results A total of 165 active ingredients and 2529 corresponding targets in Juanbi decoction were obtained from TCMSP database,and 115 targets were obtained from the intersection of drug efficacy targets and therapeutic targets of osteoarthritis,including key ingredients such as quercetin,kaempferol,naringenin,etc,and core targets such as STAT3,TNF,MAPK14,etc.GO enrichment analysis yielded 2306 biological process items,144 molecular function items and 69 cellular ingredient items;KEGG enrichment analysis yielded TNF signaling pathway,IL-17 signaling pathway,PI3K-AKT signaling pathway and other related pathways.The results of molecular docking showed that quercetin,kaempferol,naringenin,licochalcone A and formononetin were the key ingredients of Juanbi decoction in the treatment of osteoarthritis,which had good binding properties with their corresponding core targets.Conclusion Juanbi decoction may play a role in the treatment of osteoarthritis through the interaction of multiple ingredients,multiple targets and multiple pathways.