基于网络药理学及分子对接技术探讨追风透骨胶囊对类风湿关节炎和骨关节炎“异病同治”的潜在分子机制

Exploration on the Potential Molecular Mechanism of Zhuifeng Tougu Capsules in Treating Different Diseases Such as Rheumatoid Arthritis and Osteoarthritis with the Same Method Based on Network Pharmacology and Molecular Docking Technology

目的利用网络药理学方法及分子对接的方法预测追风透骨胶囊治疗类风湿关节炎(rheumatoid arthritis,RA)及骨关节炎(osteoarthritis,OA)的活性成分、作用靶点及相关生物学途径,丰富其异病同治的科学内涵。方法利用TCMSP、BATMAN-TCM数据库筛选出追风透骨胶囊的活性成分及治疗RA及OA的对应靶点,采用Cytoscape 3.7.0软件构建"药物-化合物-共有靶标"网络图,运用STRING平台构建靶蛋白相互作用(protein-protein interaction,PPI)网络,运用R语言数据包进行基因本体功能富集(gene ontology,GO)与京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomics,KEGG)富集分析,预测其作用机制,最后对追风透骨胶囊中的关键活性化合物与PPI中的核心蛋白进行分子对接验证。结果追风透骨胶囊共筛选有效活性成分276种,涉及共同靶标207个。"药物-化合物-共有靶标"网络图中筛选出关键活性化合物12个,其干预的PPI网络主要涉及STAT3、AKT1、APP等核心蛋白,共有靶标的GO及KEGG富集分析结果主要涉及代谢、炎性反应、肿瘤等相关通路及多种生物学途径。分子对接验证提示β-谷甾醇与核心靶蛋白结合情况最佳,HSP90AA1是追风透骨胶囊中关键化学成分结合活性最优的靶蛋白。结论追风透骨胶囊中槲皮素、木犀草素、山奈酚等12种关键有效活性成分作用于STAT3、AKT1、APP等12种核心靶蛋白发挥干预OA、RA的药理作用并涉及多种生物学途径,阐释了追风透骨胶囊对OA以及RA异病同治的分子基础。

Objective To predict active components, action targets and relevant biological processes of Zhuifeng Tougu Capsules in treatment of rheumatoid arthritis(RA) and osteoarthritis(OA) by means of network pharmacology and molecular docking, and to enrich its scientific connotation of treating different diseases with the same method. Methods TCMSP, BATMAN-TCM databases were applied to screen the active components of Zhuifeng Tougu Capsules and the corresponding targets in the treatment for RA and OA. Cytoscape 3.7.0 software was used to construct a network diagram of"drug-compound-common target", and the STRING platform was used to construct a target protein-protein interaction(PPI) network. The R Datasets Package was applied for gene oncology(GO) and Kyoto Encyclopedia of Genes and Genomics(KEGG) enrichment analyses to predict its mechanism of action. Finally, key active compounds of Zhuifeng Tougu Capsules and core proteins in the PPI were verified by molecular docking. Results A total of 276 active components of Zhuifeng Tougu Capsules were screened out, involving 207 common targets. Twelve key active compounds were screened out from the"drug-compound-common target"network diagram. The PPI network intervened by it mainly involved the core proteins such as STAT3, AKT1 and APP. Results in the GO and KEGG enrichment analyses on the common targets mainly involved relevant pathways and multiple biological processes like metabolism,inflammatory response and tumors. The molecular docking verification indicated that β-sitosterol could best bind to the core target proteins, HSP90 AA1 was a target protein with the best binding activity among the key chemical components in Zhuifeng Tougu Capsules. Conclusion Twelve key active components such as quercetin, luteolin and kaempferol act on 12 core target proteins such as STAT3, AKT1 and APP to play a pharmacological role on intervening OA and RA,which involves a variety of biological processes, explaining the molecular basis of Zhuifeng Tougu Capsules in treating different diseases such as OA and RA with the same method.