目的 基于网络药理学和分子对接方法探讨薏苡附子散治疗类风湿性关节炎(RA)及慢性心力衰竭(CHF)"异病同治"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)数据库筛选薏苡附子散的活性成分,并利用 Pubchem 数据库获得 Smile 号,进而通过 Swiss Target Prediction 数据库获取活性成分对应的靶点。在 GeneCards 和 OMIM数据库平台预测 RA 及 CHF 疾病作用靶点。对活性成分靶点与疾病交集靶点进行蛋白质相互作用(PPI)网络构建及核心靶点筛选,并进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。筛选核心成分和核心靶点,利用 AutoDock 软件进行分子对接验证。结果 从薏苡附子散中共筛选得到符合条件的活性成分 10 个,活性成分潜在作用靶点 403 个,RA 疾病靶点 1 112 个,CHF 疾病靶点 2 983 个,取交集,获得药物、疾病交集靶点 69 个。GO 富集分析结果显示主要与炎症反应的调节、MAPK 级联调控、对氧化应激的反应、骨化的调节、平滑肌细胞增殖等相关;KEGG 通路富集分析得到 236 条通路,与RA及CHF相关且排序较靠前的通路有 PI3K-Akt 信号通路、NF-κB 信号通路、MAPK 信号通路等。分子对接结果表明,薏苡附子散中的核心成分多根乌头碱、水黄皮素、豆甾醇具有与核心靶点 TNF、SRC、ESR1 和 PTGS2良好的结合潜力。结论 薏苡附子散治疗 RA 和 CHF 具有多靶点效应,涉及多条生物过程和信号通路,可能通过调控炎症反应、氧化应激反应、血管生成和发育、心脏收缩调节及 MAPK 级联调控等发挥"异病同治"作用。

Objective To explore the mechanism of Yiyi Fuzi Powder in treating rheumatoid arthritis (RA) and chronic heart failure (CHF) based on network pharmacology and molecular docking method. Methods The active components of Yiyi Fuzi Powder were screened by TCMSP database, and Smile number was obtained by Pubchem database, then the targets were obtained by Swiss TargetPrediction Database. The disease targets were predicted by GeneCards and OMIM database. Protein-protein interaction (PPI) network was constructed and core targets were screened, and GO function and KEGG enrichment were analyzed. After screening the core components and core targets, AutoDock software was used for molecular docking verification. Results A total of 10 compatible active components were screened, 403 potential drug targets, 1 112 targets for RA, 2 983 targets for CHF, and 69 drug-disease intersection targets were screened after the intersection. The results of GO enrichment analysis showed that it was mainly related to the regulation of inflammatory response, MAPK cascade regulation, response to oxidative stress, regulation of ossification, smooth muscle cell proliferation, etc. The enrichment analysis of KEGG pathway obtained 236 pathways. The pathways related to RA and CHF and ranked higher are PI3K-Akt signal pathway and NF-κB signal path, MAPK signal path, etc. The results of molecular docking showed that the core components of Yiyi Fuzi Powder, such as karakoline, karanjin, stigmasterol, had good binding potential with target genes TNF, SRC, ESR1 and PTGS2. Conclusion Yiyi Fuzi Powder has a multiple target effect in the treatment of RA and CHF, involving multiple biological processes and signal pathways, which may play the role of "treating different diseases with the same therapy" by regulating inflammatory response, oxidative stress response, angiogenesis and development, cardiac contraction regulation and MAPK cascade regulation.

R285.5

国家自然科学基金资助项目(81903938);国家中医药管理局青年岐黄学者项目