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.
Zhonghua Nan Ke Xue. 2024 Jan;30(1):51-59.
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.
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.
A total of 99 active components, 250 targets of YTP, 4 397 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 promoter Ⅱ, 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.
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.
基于网络药理学技术分析益肾通络方(YTP)治疗男性不育症的主要活性成分及潜在分子机制。
在中药系统药理学数据库和中医分子机制生物信息学分析工具中检索并整理YTP的主要活性成分及其各自潜在靶点,在Genecards、DisGeNET和OMIM数据库中筛选与男性不育症相关的靶点。通过将YTP的预测靶点与男性不育症的靶点进行交叉绘制韦恩图,分别使用Cytoscape软件和STRING平台构建交叉靶点与蛋白质-蛋白质相互作用(PPI)关联的可视化网络,并分别使用DAVID数据库和R语言“Cluster Profiler”软件包进行基因本体(GO)和KEGG富集分析。
共鉴定出99种活性成分、YTP的250个靶点、男性不育症的4397个靶点以及127个共同靶点。GO分析显示,共同靶点的生物学过程主要包括RNA聚合酶Ⅱ启动子的转录调控、基因表达调控、细胞凋亡调控、对雌激素的反应以及细胞对缺氧的反应。KEGG分析表明,共同靶点在雌激素信号通路、细胞凋亡通路、糖尿病并发症中的AGE-RAGE信号通路和TNF信号通路中显著富集。
通过网络药理学,我们确定了YTP治疗男性不育症的主要活性成分及其多靶点、多途径机制,为验证YTP对男性不育症作用机制的动物和细胞实验奠定了基础。