基于网络药理学和分子对接探讨补肾宁心方治疗早发性卵巢功能不全的作用机制  

Study on the mechanism of Bushen Ningxin Decoction in the treatment of premature ovarian insufficiency based on network pharmacology and molecular docking

作　　者：郭倩 马蔚蓉[1] 陈婕 王海丹[2] 谈勇[3] GUO Qian;MA Weirong;CHEN Jie;WANG Haidan;TAN Yong(Department of Gynecology,Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China;Laboratory of Basic Pharmacology,Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China;Department of Reproductive Medicine,Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]江苏省中医院妇科,江苏南京210029 [2]江苏省中医院基础药理实验室,江苏南京210029 [3]江苏省中医院生殖医学科,江苏南京210029

出　　处：《空军军医大学学报》2025年第4期483-492,共10页Journal of Air Force Medical University

基　　金：第四批江苏省名老中医药专家传承工作室建设项目(苏中医科教〔2021〕7号);江苏省卫生健康发展研究中心横向课题(JSHD202330)。

摘　　要：目的探讨补肾宁心方治疗早发性卵巢功能不全(POI)的作用靶点。方法通过对TCMSP、BATMAN-TCM数据库的检索获得补肾宁心方中各药物的活性成分,POI疾病的靶点通过GeneCards、OMIM、PharmGKB和DrugBank数据库采集,随后将活性成分与疾病基因靶点取交集,得到补肾宁心方治疗POI的预测靶点。利用Cytoscape 3.8.0构建“药物成分靶点疾病”网络;运用STRING数据库和Cytoscape构建蛋白质蛋白质相互作用网络,并对核心网络进行了精简;运用R软件进行GO富集和KEGG通路富集分析,将网络中的度值较高的成分与核心靶点进行分子对接。结果筛选出140个主要活性成分,涉及272个基因靶点,其中主要活性成分包括山柰酚、木樨草素、槲皮素、隐丹参酮、丹参酮Ⅱa、谷甾醇、豆甾醇、当归素等;核心靶点基因包括STAT3、TP53、ESR1、AKT1、MAPK1、RELA等;富集到GO生物过程2711个、细胞组分102个、分子功能293个,包括流体剪切应力和动脉粥样硬化、MAPK、TNF、IL-17等KEGG信号通路188条。分子对接结果表明,主要活性成分与核心靶点间具有较好的结合活性。结论补肾宁心方治疗POI可能是通过山柰酚、木樨草素、槲皮素、隐丹参酮、丹参酮Ⅱa、谷甾醇、豆甾醇、当归素等活性成分作用于STAT3、TP53、ESR1、AKT1、MAPK1、RELA等核心靶点,通过流体剪切应力和动脉粥样硬化、MAPK、TNF、IL-17等信号通路发挥作用。Objective To explore the therapeutic targets of Bushen Ningxin Decoction in the treatment of premature ovarian insufficiency(POI).Methods The active ingredients of each drug in Bushen Ningxin Decoction were obtained by searching TCMSP and BATMAN-TCM databases.The disease targets of POI were collected through GeneCards,OMIM,PharmGKB and DrugBank databases.The active ingredients and disease gene targets were intersected to obtain the predicted targets of Bushen Ningxin Decoction in the treatment of POI.Cytoscape 3.8.0 was used to construct the“drug component target disease”network.The protein-protein interaction network was constructed by STRING database and Cytoscape,and the core network was simplified.R software was used for GO enrichment and KEGG pathway enrichment analysis.The components with higher degree in the network were subjected to molecular docking with core targets.Results A total of 140 major active ingredients were screened,involving 272 gene targets.The major active ingredients included kaempferol,luteolin,quercetin,cryptotanshinone,tanshinone IIa,sitosterol,stigmasterol,and angelicin.The core target genes included STAT3,TP53,ESR1,AKT1,MAPK1,RELA,etc.A total of 2711 GO biological processes,102 cellular components and 293 molecular functions were enriched,including 188 KEGG signaling pathways such as fluid shear stress and atherosclerosis,MAPK,TNF,and IL-17.The results of molecular docking showed that the main active ingredients had good binding activity with the core targets.Conclusion Bushen Ningxin Decoction acts on key targets like STAT3,TP53,ESR1,AKT1,MAPK1,and RELA through active ingredients such as kaempferol,luteolin,quercetin,cryptotanshinone,tanshinone IIa,sitosterol,stigmasterol and angelicin,playing a role through fluid shear stress and atherosclerosis,MAPK,TNF,IL-17 and other signaling pathways in the treatment of POI.

关 键 词：补肾宁心方 早发性卵巢功能不全 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]