Department of Orthopaedics and Traumatology, The First Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China.
Biomed Res Int. 2020 Dec 7;2020:6971503. doi: 10.1155/2020/6971503. eCollection 2020.
To explore the molecular mechanism of Simiao powder in the treatment of knee osteoarthritis.
Based on oral bioavailability and drug-likeness, the main active components of Simiao powder were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). GeneCard, OMIM, DisGeNET, DrugBank, PharmGkb, and the Therapeutic Target Database were used to establish target databases for knee osteoarthritis. Cytoscape software was used to construct a visual interactive network diagram of "active ingredient - action target - disease." The STRING database was used to construct a protein interaction network and analyze related protein interaction relationships. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analysis were performed on the core targets. Additionally, Discovery Studio software was used for molecular docking verification of active pharmaceutical ingredients and disease targets.
Thirty-seven active components of Simiao powder were screened, including 106 common targets. The results of network analysis showed that the targets were mainly involved in regulating biological processes such as cell metabolism and apoptosis. Simiao powder components were predicted to exert their therapeutic effect on the AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway. The molecular docking results showed that the active components of Simiao powder had a good match with the targets of IL1B, MMP9, CXCL8, MAPK8, JUN, IL6, MAPK1, EGF, VEGFA, AKT1, and PTGS2.
Simiao powder has multisystem, multicomponent, and multitarget characteristics in treating knee osteoarthritis. Its possible mechanism of action includes inhibiting the inflammatory response, regulating immune function, and resisting oxidative stress to control the occurrence and development of the disease. Quercetin, wogonin, kaempferol, beta-sitosterol, and other active ingredients may be the material basis for the treatment of knee osteoarthritis.
探讨四妙丸治疗膝骨关节炎的分子机制。
基于口服生物利用度和类药性，采用中药系统药理学数据库和分析平台（TCMSP）筛选四妙丸的主要活性成分。利用 GeneCard、OMIM、DisGeNET、DrugBank、PharmGkb 和治疗靶点数据库建立膝骨关节炎靶点数据库。采用 Cytoscape 软件构建“活性成分-作用靶点-疾病”可视化互作网络图。利用 STRING 数据库构建蛋白质相互作用网络，并分析相关蛋白互作关系。对核心靶点进行京都基因与基因组百科全书（KEGG）通路和基因本体论（GO）生物过程富集分析。同时，采用 Discovery Studio 软件对活性药物成分和疾病靶点进行分子对接验证。
筛选出四妙丸的 37 个活性成分，包括 106 个共有靶点。网络分析结果表明，这些靶点主要参与调节细胞代谢和凋亡等生物过程。四妙丸成分可能通过调节 AGE-RAGE 信号通路在糖尿病并发症、IL-17 信号通路、TNF 信号通路、Toll 样受体信号通路和 HIF-1 信号通路中发挥治疗作用。分子对接结果表明，四妙丸活性成分与 IL1B、MMP9、CXCL8、MAPK8、JUN、IL6、MAPK1、EGF、VEGFA、AKT1 和 PTGS2 等靶点具有良好的匹配性。
四妙丸治疗膝骨关节炎具有多系统、多成分、多靶点的特点。其作用机制可能包括抑制炎症反应、调节免疫功能、抵抗氧化应激，从而控制疾病的发生和发展。槲皮素、汉黄芩素、山柰酚、β-谷甾醇等活性成分可能是治疗膝骨关节炎的物质基础。
