Ding Jin, Zheng Pan, Sun Ying-Ying, Wang Xiao-Ran, Feng Yan-Chen
Traditional Chinese Medicine School, Henan University of Chinese Medicine Zhengzhou 450046, China.
Prescription Discipline, Henan University of Chinese Medicine Zhengzhou 450046, China.
Zhongguo Zhong Yao Za Zhi. 2022 Aug;47(15):4164-4176. doi: 10.19540/j.cnki.cjcmm.20220412.401.
The present study explored the material basis and underlying mechanism of Wumei Pills in the treatment of ulcerative colitis(UC), diabetic enteropathy(DE), and irritable bowel syndrome(IBS) based on network pharmacology and molecular docking.The active components and targets of Wumei Pills were obtained and screened out from TCMSP, and the target names were standardized by UniProt.The related targets of UC, DE, and IBS were searched from GeneCards, DisGeNET, DrugBank, and OMIM.The Venn dia-gram was constructed using the Venny 2.1 online analysis tool to obtain the common targets of the drug and diseases.The "drug-active ingredient-target" network was constructed by Cytoscape 3.7.2.Gene Ontology(GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of common targets were carried out by DAVID.The main active components and targets were docked by AutoDock.The therapeutic mechanism of Wumei Pills was presumedly related to the regulation of the cancer pathway, TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, etc.The results of molecular docking showed that the main active components could bind to the core targets, possessing stable conformation.The therapeutic effects of Wumei Pills against three diseases involved a variety of compounds such as flavonoids, sterols, and alkaloids in the prescriptions, which acted on key targets through multiple organs and participated in multiple signaling pathways such as apoptosis and immune inflammation, thereby exerting the therapeutic action on different diseases with the same method.This study explained the underlying mechanism of Wumei Pills in "treating different diseases with same method", and is expected to provide a theoretical basis for further understanding the mechanism of Wumei Pills and exploring the new clinical application.
本研究基于网络药理学和分子对接技术，探讨乌梅丸治疗溃疡性结肠炎（UC）、糖尿病性肠病（DE）和肠易激综合征（IBS）的物质基础及潜在机制。从中药系统药理学数据库与分析平台（TCMSP）中获取并筛选出乌梅丸的活性成分和靶点，通过通用蛋白质数据库（UniProt）对靶点名称进行标准化。从基因卡片数据库（GeneCards）、疾病基因数据库（DisGeNET）、药物银行数据库（DrugBank）和在线孟德尔人类遗传数据库（OMIM）中检索UC、DE和IBS的相关靶点。使用Venny 2.1在线分析工具构建维恩图，以获得药物与疾病的共同靶点。利用Cytoscape 3.7.2构建“药物-活性成分-靶点”网络。通过DAVID对共同靶点进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析。使用自动对接软件（AutoDock）对主要活性成分和靶点进行对接。推测乌梅丸的治疗机制与癌症通路、肿瘤坏死因子（TNF）信号通路、低氧诱导因子-1（HIF-1）信号通路、磷脂酰肌醇-３激酶-蛋白激酶B（PI3K-Akt）信号通路、核因子-κB（NF-κB）信号通路、Toll样受体信号通路、Janus激酶-信号转导和转录激活因子（JAK-STAT）信号通路等的调节有关。分子对接结果表明，主要活性成分能够与核心靶点结合，具有稳定的构象。乌梅丸对三种疾病的治疗作用涉及方剂中的多种化合物，如黄酮类、甾醇类和生物碱类，这些化合物通过多个器官作用于关键靶点，并参与凋亡和免疫炎症等多种信号通路，从而以相同的方法对不同疾病发挥治疗作用。本研究阐释了乌梅丸“异病同治”的潜在机制，有望为进一步理解乌梅丸的作用机制及探索新的临床应用提供理论依据。
