基于网络药理学及分子对接探讨四妙汤治疗类风湿关节炎的作用机制

Mechanisms of Simiao Decoction in Treatment of Rheumatoid Arthriti Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学及分子对接探讨四妙汤治疗类风湿关节炎(rheumatoid arthritis, RA)的潜在活性成分及可能的分子机制。方法：使用药理学数据库(TCMSP)，预设生物利用度(OB) ≥ 30%，类药性(DL) ≥ 0.18，分别检索并筛选出四妙汤的有效成分及作用靶点，结合uniprot数据库确定标准化靶点的基因名称，利用GeneCard、OMIM、PharmGkb、TTD及DrugBank数据库，获取RA疾病靶点，制作RA疾病与四妙汤有效成分的相交靶点韦恩图，筛选出共同靶点，并以此为桥梁，采用CytoScape 3.9.1软件构建中药复方调控网络，通过数据库平台STRING 11.5绘制PPI网络图，运用R软件包clusterProfiler对治疗RA的核心靶点进行GO、KEGG富集分析。分子对接预测有效成分和靶点的结合活性。结果：筛选出四妙汤有效成分111种，相应基因靶点235个，RA差异基因3968个，靶点3824个。四妙汤治疗RA的潜在靶点144个，其中关键靶点为EGFR、FOS、TP53、MAPK3、STAT3等。KEGG富集分析显示关键信号通路包括AGE-RAGE、PI3k-Akt、IL-17、TNF、HIF-1等信号通路。分子对接结果显示槲皮素(quercetin)、山奈酚(kaempferol)、柚皮素(naringenin)、甘草查尔酮A (licochalcone a)、木犀草素(luteolin)等可能是四妙汤治疗RA的核心活性成分。结论：四妙汤多成分、多靶点、多通路协同机制治疗RA，和癌症相关通路、脂质与动脉粥样硬化、氧化应激、炎症信号通路、病毒感染等机制密切相关。

Abstract: Objective: This study aimed to explore the potential active ingredients and possible molecular mechanisms of Simiao Decoction for rheumatoid arthritis (RA) treatment based on network pharmacology and molecular docking. Methods: We use the pharmacological database (TCMSP) and the active ingredients and action targets of Simiao Decoction were retrieved and screened by preset bioavailability (OB) ≥ 30% and drug resistance (DL) ≥ 0.18, the “uniprot” database was used to determine the gene names of the normalized targets, and the GeneCard, OMIM, PharmGkb, TTD and DrugBank databases were used to obtain the RA disease targets to produce the intersectional targets Venn diagram of RA diseases and the active ingredients of Simiao decoction, and the common targets were screened, the regulatory network of TCM compound was constructed by CytoScape 3.9.1 software, PPI network diagram was drawn by database platform STRING 11.5 and GO, KEGG enrichment analysis of core targets for the treatment of RA was performed using R package clusterProfiler. Molecular docking predicts the binding activity of active ingredients and targets. Results: A total of 111 active ingredients of Simiao decoction were screened, including 235 corresponding gene targets, 3968 RA differential genes and 3824 targets. There are 144 potential targets of Simiao Decoction in the treatment of RA, among which the key targets are EGFR, FOS, TP53, MAPK3 and STAT3. KEGG enrichment analysis shows that key signal pathways include AGE-RAGE, PI3k-Akt, IL-17, TNF, HIF-1, etc. Molecular docking results showed that the crucial active ingredients of Simiao Decoction in the treatment of RA might be quercetin, kaempferol, naringenin, Lico-chalcone a, and luteolin. Conclusion: This study reveals that Simiao Decoction may act on RA through multi component, multi target, multi pathway synergistic mechanism, which is closely related to cancer-related pathways, lipids and atherosclerosis, oxidative stress, inflammatory signaling pathways, viral infection and other mechanisms are closely related.