Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Key Laboratory of Chinese Medicine Compound and Chinese Medicine Resources Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China.
Comb Chem High Throughput Screen. 2023;26(1):30-48. doi: 10.2174/1386207325666220221121919.
Wu-Mei-Wan (WMW), a traditional Chinese medicine (TCM) formula, has a good effect on the treatment of obesity and has been proven helpful to promote the metabolism of adipose tissue. However, its underlying mechanism remains to be studied. This study aims to explore the potential pharmacological mechanism of WMW in the treatment of obesity.
Network pharmacology was used to sort out the relationship between WMW putative targets and obesity-related drug targets or disease targets, which indicated the mechanism of WMW in treating obesity from two aspects of clinical drugs approved by the Food and Drug Administration (FDA) and obesity-related diseases. Databases such as Traditional Chinese Medicine Systems Pharmacology (TCMSP), PubChem, DrugBank, DisGeNET, and Genecards were used to collect information about targets. String platform was used to convert the data into gene symbol of "homo sapiens", and perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. With the Human Protein Reference Database (HPRD) as background data, Cytoscape 3.6.0 software was used to construct a new protein-protein interaction (PPI) network. Mechanism diagrams of key pathways were obtained from the KEGG database. AutoDock Vina software was used to conduct molecular docking verification.
The number of targets in the overlap between WMW putative targets and obesity-related drug targets accounted for more than 50% of the latter, and HTR3A, SLC6A4, and CYP3A4 were core targets. In obesity-related disease targets-WMW putative targets PPI network, the Th17 cell differentiation pathway, and the IL-17 signaling pathway were key pathways, and the 1st module and the 7th module were central function modules that were highly associated with immunity and inflammation. Molecular docking verified that STAT3, TGFB1, MMP9, AHR, IL1B, and CCL2 were core targets in the treatment of WMW on obesity.
WMW has similar effects on lipid and drug metabolism as the current obesity-related drugs, and is likely to treat obesity by inhibiting Th17 cell differentiation and alleviating metabolic inflammation.
乌梅丸（WMW）是一种中药方剂，对肥胖症的治疗有很好的效果，已被证明有助于促进脂肪组织的新陈代谢。然而，其潜在的作用机制仍有待研究。本研究旨在探讨 WMW 治疗肥胖的潜在药理学机制。
采用网络药理学方法整理 WMW 假定靶点与肥胖相关药物靶点或疾病靶点之间的关系，从 FDA 批准的临床药物和肥胖相关疾病两个方面探讨 WMW 治疗肥胖的作用机制。TCMSP、PubChem、DrugBank、DisGeNET 和 Genecards 等数据库用于收集目标信息。String 平台将数据转换为“智人”的基因符号，并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。以人类蛋白质参考数据库（HPRD）为背景数据，使用 Cytoscape 3.6.0 软件构建新的蛋白质-蛋白质相互作用（PPI）网络。从 KEGG 数据库中获得关键途径的机制图。使用 AutoDock Vina 软件进行分子对接验证。
WMW 假定靶点与肥胖相关药物靶点重叠的靶点数量占后者的 50%以上，HTR3A、SLC6A4 和 CYP3A4 是核心靶点。在肥胖相关疾病靶点-WMW 假定靶点 PPI 网络中，Th17 细胞分化途径和 IL-17 信号通路是关键通路，第 1 模块和第 7 模块是与免疫和炎症高度相关的核心功能模块。分子对接验证了 STAT3、TGFB1、MMP9、AHR、IL1B 和 CCL2 是 WMW 治疗肥胖的核心靶点。
WMW 对脂质和药物代谢的作用与目前的肥胖相关药物相似，可能通过抑制 Th17 细胞分化和缓解代谢性炎症来治疗肥胖。
