基于网络药理学和分子对接技术探讨杞贞滋阴合剂治疗性腺功能减退症的作用机制

Mechanism of Qizhenziyin mixture in the treatment of hypogonadism based on network pharmacology analysis and molecular docking

目的 应用网络药理学研究杞贞滋阴合剂治疗性腺功能减退症的作用机制。方法 检索中药系统药理学数据库与分析平台(TCMSP)、中药综合数据库(TCMID)、药物成分靶标数据库(HIT)获取杞贞滋阴合剂的化学成分,从蛋白质-化学相互作用网络数据库(STITCH)中收集候选化合物的相关靶点。利用GeneCards和DisGeNet数据库对性腺功能减退症的疾病基因进行映射,获得杞贞滋阴合剂治疗性腺功能减退症的潜在靶点。通过蛋白互作平台数据库(STRING)构建作用靶点之间的互作关系(PPI),将其导入Cytoscap软件构建PPI网络图。最后,通过对靶点基因进行GO、KEGG富集分析和分子对接,分析杞贞滋阴合剂治疗性腺功能减退症的作用机制。结果 共获得148种疾病与药物交集化合物、96个疾病与药物交集靶点、1 085个疾病靶点;其中,与疾病相关的成分有槲皮素、山柰酚、木犀草素等;通过GO富集分析共得到生物过程(BP)1 792条、细胞组成(CC)31条、分子功能(MF)79条;通过KEGG富集分析得到FOXO通路、前列腺癌症通路、糖尿病并发症中的AGE-RAGE信号通路、HIF-1通路等;通过分子对接显示,LEP与山柰酚的结合力最好也最稳定。结论 杞贞滋阴合剂的活性成分可能是通过改善胰岛素抵抗和Leydig细胞睾酮合成酶表达来发挥治疗性腺功能减退症的作用。

Objective To investigate the mechanism of Qizhenziyin mixture in the treatment of hypogonadism by using the network pharmacology approach.Methods The active components of Qizhenziyin mixture were obtained by searching TCMSP,TCMID and HIT databases.The related targets of candidate compounds were obtained by searching STITCH databases.The potential targets of Qizhenziyin mixture in the treatment of hypogonadism were obtained by mapping the disease genes of hypogonadism with Genecards and DisGeNet databases.The protein interaction platform database(STRING)was used to construct the interaction relationship between action targets.The target protein interaction(PPI)network was constructed by introducing Cytoscape software.The mechanism of Qizhenziyin mixture in the treatment of hypogonadism was explained through the enrichment analysis of GO,KEGG and molecular docking technology.Results A total of 148 drug-disease chemical compounds,96 drug-disease intersection targets,1085 disease targets were obtained;the components for treating diseases are:quercetin,kaempferol,luteolin,etc;enrichment analysis of GO revealed 1792 biological processes(BP),31 cellular components(CC)and 79 molecular functions(MF);the results of KEGG pathway enrichment analysis indicated such as FOXO signaling pathway,prostate cancer,AGE-RAGE signaling pathway in diabetic complications,HIF-1 signaling pathway,etc.The results of molecular docking showed that kaempferol and LEP had the best and stable binding energy.Conclusion The active components of Qizhenziyin mixture may play a role of the treatment of hypogonadism by improving insulin resistance and the expression of testosterone synthetase of Leydig cells.