基于网络药理学探究黄柏治疗尿酸性肾病的分子机制

Exploring the Molecular Mechanism of Phellodendron in Treating Uric Acid Nephropathy Based on Network Pharmacology

摘要: 目的：通过网络药理学方法研究黄柏治疗尿酸性肾病(uric acid nephropathy, UAN)的分子机制。方法：借助中药系统药理学数据库与分析平台(TCMSP)和Swiss Target Prediction获得黄柏的活性成分及对应靶点，利用GeneCards数据库和在线人类孟德尔遗传数据库(OMIM)获取UAN的相关靶点。使用Venn2.1.0平台得到相应药物靶点与疾病靶点的交集并将其导入String数据库以构建蛋白相互作用网络，然后将PPI网络导入Cytoscape3.9.1软件构建“药物–有效成分–靶点”，筛选可能发挥治疗作用的核心靶点，将交集靶点导入Metascape数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)信号通路富集分析获知其潜在的作用机制，并在微生信进行可视化处理。结果：药物共筛选到20个有效成分并得到554个靶点。得到UAN的靶点共1540个，其中交集靶点172个。PPI网络筛选出核心靶点33个。经GO分析和KEGG分析，表明黄柏可能主要通过调控多条信号通路抑制尿酸的合成、降低肾脏中炎症因子表达的作用来对UAN起到治疗作用。结论：本研究运用网络药理学的分析方法预测黄柏治疗UAN可能的活性成分、关键靶点及作用通路，体现中药治疗疾病具有“多成分、多靶点、多途径”的特点，为其药效物质基础和作用机制研究提供理论基础，印证临床上运用黄柏治疗UAN的可行性。

Abstract: Objective: To investigate the molecular mechanism of Phellodendron in the treatment of uric acid nephropathy (UAN) by network pharmacology methods. Methods: The active components and corresponding targets of Phellodendron were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and Swiss Target Prediction. The targets of UAN were obtained from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The intersection of drug targets and disease targets was obtained using the Venn2.0.1 platform and imported into the String database to construct a protein-protein interaction network, which was then imported into Cytoscape3.9.1 software to construct a “drug-active component-target” network. The core targets were screened, and the intersection targets were imported into Metascape database for gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to reveal their potential mechanisms of action, which were then visualized in MicroHIS. Results: A total of 20 effective components were identified, and 554 targets were obtained. A total of 1540 targets of UAN were obtained, including 172 intersection targets. 33 core targets were selected from the PPI network. GO analysis and KEGG analysis showed that Phellodendron may mainly regulate multiple signaling pathways to inhibit the synthesis of uric acid and reduce the expression of inflammatory factors in the kidney to treat UAN. Conclusion: This study uses network pharmacology analysis methods to predict the active components, key targets, and action pathways of Huangbo in the treatment of UAN, reflecting the characteristics of traditional Chinese medicine in treating diseases, such as “multiple components, multiple targets, and multiple pathways”. It provides a theoretical basis for the study of the pharmacological effects and mechanisms of action of Phellodendron, and confirms the feasibility of clinically using Phellodendron to treat UAN.