基于网络药理学探讨五积散治疗多囊卵巢综合征的靶点和作用机制

doi:10.5246/jcps.2024.10.069

摘要/Abstract

摘要：

为了探讨五积散治疗PCOS的潜在作用机制, 本研究通过中药系统药理数据库和分析平台(TCMSP)筛选出五积散中各药物的活性成分, 并对五积散活性成分进行靶点预测; 在GeneCards数据库查询与PCOS相关的基因, 于在线网站(http://bioinformatics.psb.ugent.be/webtools/Venn/)对药物靶点和疾病靶点取交集, 以共同基因作为五积散治疗PCOS的作用靶点; 通过String网站构建蛋白质互作(PPI)网络图, 用Cytoscape3.7.1软件筛选PPI网络图的关键蛋白模块及Hub基因; 在DAVID数据库对关键模块包含的基因进行GO功能注释和KEGG通路富集分析。最终, 共筛选出五积散治疗PCOS的活性成分63个, 匹配到266个药物靶点; 检索到PCOS的疾病靶点2575个, 取交集后得到PCOS的作用靶点174个。共识别出10个关键模块, 筛选出10个Hub基因(TNF、MMP9、AKT1、ECG、VEGFA、PTGS2、IL-6、MAPK3、STAT3、CXCL8)。KEGG通路富集得到58个信号通路, 如TNF、MAPK、PI3K-Akt信号通路等; GO功能注释得到5个细胞组分(CC), 包括细胞外空间、细胞外区域、血小板α颗粒管腔、小凹、蛋白质细胞外基质; 9个分子功能(MF), 包括酶结合、细胞因子活性、相同的蛋白质结合、生长因子活性、转录因子结合、蛋白酶结合、MAP激酶活性、蛋白磷酸酶结合、蛋白质结合; 58个生物学过程(BP), 主要集中于药物反应、RNA聚合酶II启动子转录的正调控、脂多糖介导的信号通路、对雌二醇的反应、趋化因子生物合成过程的正调控、MAPK级联、炎症反应等。这提示五积散可能主要通过调控TNF/PI3K/AKT信号通路, 发挥治疗PCOS作用。

关键词: 多囊卵巢综合征, 网络药理学, 五积散, 炎症, 胰岛素抵抗

Abstract:

To elucidate the potential mechanism of Wuji powder in treating polycystic ovary syndrome (PCOS), this study utilized TCMSP database to screen the active ingredients of each constituent drug in Wuji powder. Subsequently, we predicted the target proteins associated with these active ingredients. In parallel, we employed the GeneCards database to identify genes related to PCOS and determined the intersection of drug targets and disease targets using the online tool available at http://bioinformatics.psb.ugent.be/webtools/Venn/. The shared genes were considered as the target proteins of Wuji powder in the treatment of PCOS. Utilizing the String website, we constructed a protein-protein interaction (PPI) network diagram and identified key protein modules and hub genes within the PPI network using Cytoscape 3.7.1 software. Further analysis in the DAVID database involved GO and KEGG pathway enrichment analyses of the genes within the identified key modules. Our investigation revealed a total of 63 active ingredients in Wuji powder with potential therapeutic effects on PCOS, corresponding to 266 drug targets. Intersection with PCOS-related disease targets yielded 174 shared targets. Ten key modules and ten hub genes (TNF, MMP9, AKT1, ECG, VEGFA, PTGS2, IL-6, MAPK3, STAT3, and CXCL8) were identified through network analysis. KEGG pathway enrichment analysis uncovered 58 signaling pathways, including TNF, MAPK, and PI3K-Akt signaling pathways. GO functional annotation delineated five cellular components (CC), nine molecular functions (MF), and 58 biological processes (BP). Noteworthy findings included extracellular space, enzyme binding, and drug response among CC, MF, and BP categories, respectively. These results collectively suggested that Wuji powder might exert its therapeutic effects on PCOS by modulating the TNF/PI3K/AKT signaling pathway.

Key words: Polycystic ovary syndrome, Network pharmacology, Wuji powder, Inflammation, Insulin resistance

Supporting:

范文霞, 李少杰, 王芳, 李银丹, 杨金姬, 宋文广, 付浩. 基于网络药理学探讨五积散治疗多囊卵巢综合征的靶点和作用机制[J]. 中国药学(英文版), 2024, 33(10): 965-976.

Wenxia Fan, Shaojie Li, Fang Wang, Yindan Li, Jinji Yang, Wenguang Song, Hao Fu. Elucidating the mechanism of Wuji powder in polycystic ovary syndrome treatment: a network pharmacology approach[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(10): 965-976.

图/表 4

Table 1. Effective components and corresponding molecular names of Wuji powder.

Figure 1. Interaction network diagram of target proteins.

Figure 2. Key modules and hub genes of PPI network. (A)–(C) The top three key modules of MCODE score; (D) Hub gene of module A.

Figure 3. Gene function enrichment analysis results of key modules. (A) KEGG pathway enrichment analysis results; (B–D) GO analysis results of cellular components, molecular functions, and biological processes.

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