基于网络药理学探讨金匮肾气丸治疗良性前列腺增生症的潜在作用机制

Potential Mechanism of Jinkui Shenqi Pill in Treating Benign Prostatic Hyperplasia Based on Network Pharmacology

目的基于网络药理学探讨金匮肾气丸治疗良性前列腺增生症(Benign prostatic hyperplasia,BPH)的潜在作用机制。方法通过相关数据库搜集金匮肾气丸治疗BPH的有效成分、药物基因靶点信息以及BPH疾病相关基因,整理药物靶基因和疾病相关基因得到交集基因,利用交集基因筛选出其中核心有效成分。将交集基因整理得出蛋白互作网络(PPI),经过两次筛选确定核心基因网络。同时进行GO功能注释和KEGG通路富集分析,选出核心网络中Degree分值较高的核心靶点和对应的有效成分,通过数据库找出药物核心成分小分子配体和中药靶点蛋白受体,将得到的小分子配体和蛋白受体进行分子对接。结果本次研究共筛选出有效化学成分48个,155个交集靶点,核心有效成分包括β-谷甾醇、槲皮素、水黄皮素等,核心基因靶点有JUN、ESR1、MYC等11种。核心靶点基因主要通过PI3K-Akt通路、化学致癌通路、血脂与动脉粥样硬化通路等参与组织氧化应激反应、DNA结合转录因子结合、脂筏、RNA聚合酶Ⅱ特异性DNA结合转录因子结合、细胞对化学应激的反应等过程,核心成分与关键靶点能自由结合,其中JUN与β-谷甾醇结合力最强。结论金匮肾气丸治疗BPH效果明确,具有多靶点、多通路的特点,作用的主要原理可能通过β-谷甾醇作用于JUN靶点。

Objective To explore the potential mechanism of Jinkui Shenqi pill in treating BPH by network pharmacology.Methods The effective components,drug gene target information and BPH disease-related genes of Jinkui Shenqi pill in the treatment of BPH were collected through the relevant database.The drug target genes and disease-related genes were sorted to obtain the intersection genes,and the core effective components were screened out by the intersection genes.The intersection genes were sorted out to obtain a protein interaction network(PPI),and the core gene network was determined after two screenings.At the same time,GO functional annotation and KEGG pathway enrichment analysis were carried out to select the core targets and corresponding active ingredients with higher degree scores in the core network.Through the database,the small molecule ligands of the core components of the drug and the protein receptors of the target of traditional Chinese medicine were found out,and the obtained small molecule ligands and protein receptors were molecularly docked.Results A total of 48 effective chemical components and 155 intersection targets were screened out.The core effective components includedβ-sitosterol,quercetin and luteolin.The core gene targets included 11 kinds of JUN,ESR1,MYC,etc.The core target genes were mainly involved in tissue oxidative stress response,DNA binding transcription factor binding,lipid raft,RNA polymeraseⅡspecific DNA binding transcription factor binding,cell response to chemical stress through PI3K-Akt pathway,chemical carcinogenesis pathway,blood lipid and atherosclerosis pathway.The core components could freely bind to the key targets,among which JUN had the strongest binding force withβ-sitosterol.Conclusion The effect of Jinkui Shenqi pill in the treatment of BPH is clear,with the characteristics of multi-target and multi-pathway.The main mechanism may be throughβ-sitosterol acting on JUN target.