目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對接方法探討薏苡附子散治療類風(fēng)濕性關(guān)節(jié)炎(RA)及慢性心力衰竭(CHF)"異病同治"的作用機(jī)制。方法 通過中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺(TCMSP)數(shù)據(jù)庫篩選薏苡附子散的活性成分,并利用 Pubchem 數(shù)據(jù)庫獲得 Smile 號,進(jìn)而通過 Swiss Target Prediction 數(shù)據(jù)庫獲取活性成分對應(yīng)的靶點。在 GeneCards 和 OMIM數(shù)據(jù)庫平臺預(yù)測 RA 及 CHF 疾病作用靶點。對活性成分靶點與疾病交集靶點進(jìn)行蛋白質(zhì)相互作用(PPI)網(wǎng)絡(luò)構(gòu)建及核心靶點篩選,并進(jìn)行基因本體(GO)功能及京都基因與基因組百科全書(KEGG)通路富集分析。篩選核心成分和核心靶點,利用 AutoDock 軟件進(jìn)行分子對接驗證。結(jié)果 從薏苡附子散中共篩選得到符合條件的活性成分 10 個,活性成分潛在作用靶點 403 個,RA 疾病靶點 1 112 個,CHF 疾病靶點 2 983 個,取交集,獲得藥物、疾病交集靶點 69 個。GO 富集分析結(jié)果顯示主要與炎癥反應(yīng)的調(diào)節(jié)、MAPK 級聯(lián)調(diào)控、對氧化應(yīng)激的反應(yīng)、骨化的調(diào)節(jié)、平滑肌細(xì)胞增殖等相關(guān);KEGG 通路富集分析得到 236 條通路,與RA及CHF相關(guān)且排序較靠前的通路有 PI3K-Akt 信號通路、NF-κB 信號通路、MAPK 信號通路等。分子對接結(jié)果表明,薏苡附子散中的核心成分多根烏頭堿、水黃皮素、豆甾醇具有與核心靶點 TNF、SRC、ESR1 和 PTGS2良好的結(jié)合潛力。結(jié)論 薏苡附子散治療 RA 和 CHF 具有多靶點效應(yīng),涉及多條生物過程和信號通路,可能通過調(diào)控炎癥反應(yīng)、氧化應(yīng)激反應(yīng)、血管生成和發(fā)育、心臟收縮調(diào)節(jié)及 MAPK 級聯(lián)調(diào)控等發(fā)揮"異病同治"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

國家自然科學(xué)基金資助項目(81903938);國家中醫(yī)藥管理局青年岐黃學(xué)者項目