基于网络药理-分子对接技术研究当归芍药散“异病同治”妇科疾病作用机制

Study on mechanism of Danggui Shaoyao powder treating different diseases with the same treatment in gynecological diseases based on network pharmacology and molecular docking

目的:通过网络药理-分子对接方法探讨当归芍药散对闭经、不孕、多囊卵巢综合征(PCOS)“异病同治”的作用机制。方法:利用中药系统药理学分析平台(TCMSP)数据库和SEA、BATMAN和Swiss检索当归芍药散中的活性成分和作用靶点;通过GeneCards和CTD疾病数据库获取闭经、不孕和PCOS的相关基因,将两者放入Venny中提取交集放入STRING数据库构建共有靶点的PPI网络;应用Matescape进行GO功能富集和KEGG通路分析;利用Cytoscape3.8.2构建当归芍药散与闭经、不孕、PCOS的靶点关联网络;利用AutoDuck Tools将核心靶点和化合物分别进行分子对接。结果:筛选出52个当归芍药散中的有效化学成分,检索出84个基因靶点;疾病数据库得到疾病靶点705个,两者取交集后共得到30个共同靶点。中药化学成分-作用靶点网络分析发现谷甾醇(sitosterol)、β-谷甾醇(beta-sitosterol)、豆甾醇(Stigmasterol)可能是当归芍药散主要的潜在活性成分,可能作用于AR、HMGCR、HSD11B1、CYP19A1、NR3C1等靶点,GO功能富集和KEGG通路富集分析得到5个模块,涉及癌症途径、类固醇生物合成、PPAR信号通路等途径实现同病异治作用;分子对接结果显示,α-香树脂醇(α-Amyrin)与主要靶点结合具有较好的结合活性。结论:当归芍药散“异病同治”闭经、不孕和PCOS的主要机制涉及抗炎、抗氧化、降低胆固醇、癌症途径、类固醇合成与代谢、胰岛素抵抗等相关信号通路。

Objective:To explore the mechanism of Danggui Shaoyao powder treating different diseases with the same treatment in amenorrhea,infertility and polycystic ovary syndrome(PCOS)by network pharmacology and molecular docking.Method:The active components and targets of Danggui Shaoyao powder were searched by the traditional Chinese medicine systematic pharmacology(TCMSP),SEA,BATMAN and Swiss databases.The related genes of amenorrhea,infertility and PCOS were obtained by the GeneCards and CTD disease databases.Their intersection was obtained by Venny,and the PPI network of common targets was constructed by the String database.Matescape was used for GO function enrichment and KEGG pathway analysis.The target association network of Danggui Shaoyao powder with amenorrhea,infertility and PCOS was constructed by Cytoscape 3.8.2.AutoDock Tools were used for the molecular docking of the core targets with the compounds.Result:52 effective components in Danggui Shaoyao powder were screened,and 84 gene targets were retrieved.705 disease targets were obtained by the disease databases,and 30 common targets were obtained after their intersection.The analysis of traditional Chinese medicine chemical component-target network showed that sitosterol,β-sitosterol and stigmasterol might be the main potential active components of Danggui Shaoyao powder,which might act on the targets including AR,HMGCR,HSD11B1,CYP19A1 and NR3C1.Five modules were obtained by the GO enrichment and KEGG pathway enrichment analysis,involving cancer pathways,steroid biosynthesis,PPAR signaling pathway and other pathways to achieve the effect of treating different diseases with the same treatment.The results of molecular docking showed thatα-amyrin had a good activity to bind to the main targets.Conclusion:The main mechanisms of Danggui Shaoyao powder treating different diseases with the same treatment in amenorrhea,infertility and PCOS involve the signaling pathways related to anti-inflammatory,anti-oxidant,cholesterol lowering,cancer pathways,steroids synthesis and metabolism and insulin resistance.