摘要
目的:通过网络药理学技术分析益肾通络方治疗男性不育的主要有效活性成分及其潜在作用分子机制。方法:利用中药系统药理学(TCMSP)数据库与中药分子机制生物信息学分析工具(BATMAN-TCM)数据库查询整理益肾通络方中每味药物的主要活性成分与潜在靶点;使用Genecards数据库、DisGeNET、OMIM等数据库查找、筛选男性不育疾病相关靶点;将益肾通络方药物预测靶点与男性不育疾病靶点取交集,制作Venn图,借助Cytoscape软件构建交集靶点可视化联系,利用STRING平台构建蛋白互作网络(PPI),利用DAVID数据库与R语言“Cluster Profiler”软件包,进行GO功能分析与KEEG富集分析。结果:共筛选出益肾通络方主要有效活性成分99个,包含250个靶点;男性不育靶点4397个;通过Venny2.1.0取交集,共获得127个共同作用靶点;Go分析提示主要与RNA聚合酶启动子Ⅱ的转录调控、基因表达的调控、凋亡过程的调控、对雌激素的反应、细胞对缺氧的反应等生物过程和功能有关;KEGG分析提示主要显著富集于雌激素信号通路、细胞凋亡通路、糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路等。结论:通过网络药理学研究,初步揭示了益肾通络方主要有效活性成分及其治疗男性不育的多靶点-多途径作用机制,为后期动物、细胞实验验证中药复方益肾通络方治疗男性不育的作用机制奠定了基础。
Objective:To analyze the main active components and potential molecular mechanism of Yishen Tongluo Prescription(YTP)in the treatment of male infertility based on network pharmacological technology.Methods:We searched and sorted the main active components of YTP and their individual potential targets in the databases of Systematic Pharmacology of Traditional Chinese Medicine(TCM)and Bioinformatics Analysis Tool of the Molecular Mechanism of TCM,and screened the targets related to male infertility diseases in the databases of Genecards,DisGeNET and OMIM.We made a Venn diagram by intersecting the predicted targets of YTP and those of male infertility diseases,constructed visualized networks for the association of the intersection targets and protein-protein interaction(PPI)using the Cytoscape software and STRING platform respectively,and conducted gene ontology(GO)and KEGG enrichment analyses using the DAVID database and R language"Cluster Profiler"software package respectively.Results:A total of 99 active components,250 targets of YTP,4397 targets of male infertility and 127 common targets were identified.GO analysis revealed that the biological processes of the common targets mainly included transcriptional regulation of RNA polymerase promoterⅡ,regulation of gene expressions,regulation of apoptosis,responses to estrogen,and cell responses to hypoxia.KEGG analysis showed significant enrichment of the common targets in the estrogen signaling pathway,cell apoptosis pathway,AGE-RAGE signaling pathway in diabetic complications,and TNF signaling pathway.Conclusion:Through network pharmacology,we identified the main active components of YTP and its multi-target and multi-pathway mechanism in the treatment of male infertility,which has paved the ground for animal and cell experiments in verifying the action mechanism of YTP on male infertility.
作者
郝高利
孙自学
樊立鹏
徐磊
秦国政
HAO Gao-li;SUN Zi-xue;FAN Li-peng;XU Lei;QIN Guo-zheng(Department of Andrology,Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210033,China;Department of Andrology,Henan Provincial Hospital of Traditional Chinese Medicine/The Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou,Henan 450002,China;Department of Andrology,The First Affiliated Hospital of Yunnan University of Chinese Medicine,Kunming,Yunnan 650021,China;Department of Andrology,Yunnan Provincial Hospital of Traditional Chinese Medicine,Kunming,Yunnan 650021,China)
出处
《中华男科学杂志》
CAS
CSCD
2024年第1期51-59,共9页
National Journal of Andrology
基金
国家自然科学基金面上项目(82274536)
河南省重点科技攻关课题(222102310100)
河南省防治生殖障碍性疾病中医药重点实验室(2021ZDSYS10)
关键词
网络药理学
益肾通络方
男性不育
作用机制
network pharmacology
Yishen Tongluo Prescription
male infertility
action mechanism
