基于网络药理学五子衍宗丸治疗高尿酸血症的多靶点分子机制研究

Study on the Multi-Target Molecular Mechanisms of Wuzi Yanzong Wan in Treating Hyperuricemia Based on Network Pharmacology

摘要: 目的：通过网络药理学的方法分析五子衍宗丸治疗高尿酸血症的作用机制。方法：通过TCMSP数据库获取车前子、五味子、覆盆子、枸杞子、菟丝子的化学成分，经过SwissAdme进行筛选后，导入SwissTargetPrediction数据库中预测化学成分的靶点，从GeneCards、OMIM、DRUGBANK等数据库获取高尿酸血症相关基因，与前者取交集后得到交叉靶点，导入string数据库进行蛋白质相互作用分析，构建PPI网络并获取网络中蛋白质功能模块。使用cytoscape3.7.1制作活性成分–靶点网络，并利用sentiscape2.2筛选出五子衍宗丸治疗高尿酸血症的核心靶点。使用Metascape数据库对交叉靶点进行GO及KEGG富集分析。结果：得到药效成分137种，药物靶点849个，高尿酸血症疾病靶点764个，关键靶点21个，KEGG通路92条。五子衍宗丸治疗高尿酸血症的主要成分为槲皮素、山奈酚、芹菜素、粗毛豚草素等，关键靶点为PPARG、TNF、SIRT1、PTGS2、XDH，关键的生物学进程及通路可能为核苷酸代谢、胰高血糖素信号通路、AMPK信号通路、胰岛素信号通路、HIF-1 signaling pathway、酒精性肝病等。结论：本研究初步揭示了五子衍宗丸治疗高尿酸血症多成分、多靶点、多通路的作用机制，为五子衍宗丸的临床应用提供新的思路与治疗方向。

Abstract: Objective: To analyze the mechanism of action of Wuzi Yanzong Wan in the treatment of hyperuricemia using a network pharmacology approach. Methods: Chemical components of Plantaginis Semen, Schisandrae Chinensis Fructus, Rubi Fructus, Lycii Fructus, and Cuscutae Semen were retrieved from the TCMSP database. After screening with SwissADME, the components were imported into the SwissTargetPrediction database to predict their potential targets. Disease-related genes for hyperuricemia were obtained from databases including GeneCards, OMIM, and DrugBank. Intersection targets were identified by comparing the drug targets and disease targets. These intersection targets were then imported into the STRING database for protein-protein interaction (PPI) analysis to construct a PPI network and identify functional protein modules. Cytoscape 3.7.1 was used to construct an active ingredient-target network, and cytoHubba was applied to screen out the core targets for the treatment of hyperuricemia with Wuzi Yanzong Wan. The Metascape database was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the intersection targets. Results: A total of 137 active components, 849 drug targets, and 764 disease targets for hyperuricemia were identified, leading to 21 key targets and 92 KEGG pathways. The main active components of Wuzi Yanzong Wan for treating hyperuricemia included quercetin, kaempferol, apigenin, and hispidulin. The key targets were PPARG, TNF, SIRT1, PTGS2, and XDH. Key biological processes and pathways potentially involved nucleotide metabolism, the glucagon signaling pathway, AMPK signaling pathway, insulin signaling pathway, HIF-1 signaling pathway, and alcoholic liver disease. Conclusion: This study preliminarily reveals the multi-component, multi-target, and multi-pathway mechanism of Wuzi Yanzong Wan in the treatment of hyperuricemia, providing new insights and therapeutic directions for its clinical application.