乌头汤治疗骨关节炎作用机制的网络药理学研究
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篇名: 乌头汤治疗骨关节炎作用机制的网络药理学研究
TITLE:
摘要: 目的:研究乌头汤治疗骨关节炎的作用机制,为骨关节炎的治疗提供新的方向与靶点。方法:以口服生物利用度(OB)≥30%、类药性(DL)≥0.18为指标,借助中药系统药理学数据库及分析平台(TCMSP)筛选乌头汤中川乌、麻黄、黄芪、白芍与甘草的活性成分;通过检索治疗靶点数据库(TTD)等数据库和挖掘基因表达数据库(GEO)中的芯片数据获取骨关节炎的作用靶点;利用生物学信息注释数据库(DAVID)对靶点基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。结果:从乌头汤中共筛选出活性成分30个,包括槲皮素、丁子香萜、栀子醇等,与骨关节炎相关的作用靶点31个,包括β2肾上腺素能受体、花生四烯酸5-脂氧合酶、雄激素受体等。乌头汤治疗骨关节炎的生物过程与白细胞介素1受体信号转导、过氧化物酶增殖激活受体的协同激活作用、酪氨酸激酶受体2的信号转导作用等有关。乌头汤主要通过调节肿瘤坏死因子信号通路、血管内皮生长因子信号通路、破骨细胞分化信号通路、核转录因子κB信号通路、Toll样受体信号通路等发挥治疗骨关节炎的作用。结论:本研究采用网络药理学分析了乌头汤治疗骨关节炎的潜在作用机制,可为进一步研究乌头汤治疗骨关节炎的药效物质基础及作用靶点提供参考。
ABSTRACT: OBECTIVE: To study the mechanism of Wutou decoction in the treatment of osteoarthritis, and to provide a new direction and target for the treatment of osteoarthritis. METHODS: Using oral bioavailability (OB)≥30%, drug like (DL)≥0.18% as index, active components were screened from Wutou decoction by using TCM systematic pharmacological analysis platform (TCMSP), such as Aconitum carmichaelii, Ephedra sinica, Astragalus propinquus, Paeonia tactilora, Glycyrrhiza uralensis. Targets of osteoarthritis were obtained by retrieving therapeutic targets database (TTD) and mining thip data from gene expression database (GEO). Target genes were analyzed by GO and KEGG pathway enrichment analysis were performed by using DAVID database. RESULTS: A total of 30 active components were screened, including quercetin, terpenoids and gardenol; 31 targets related to osteoarthritis were obtained, including β2 adrenergic receptor, arachidonate 5-lipoxygenase and androgen receptor. The biological process of Wutou decoction in treatment of osteoarthritis was mainly related to the IL-1 receptor signal transduction, synergistic activation of peroxidase proliferation activated receptor, signal transduction of tyrosine kinase receptor 2. It mainly regulated tumor necrosis factor signaling pathway, vascular endothelial growth factor signaling pathway, osteoclasts differentiation signaling pathway, nuclear factor κB signaling pathway, Toll-like receptor signaling pathway so as to play a role in the treatment of osteoarthritis. CONCLUSIONS: The study analysis the potential mechanism of Wutou decoction in the treatment of osteoarthritis based on network pharmacology, which can provide reference for further study on the material basis and target of Wutou decoction in the treatment of osteoarthritis.
期刊: 2019年第30卷第19期
作者: 骆帝,梁学振,刘金豹,许波,李刚
AUTHORS: LUO Di,LIANG Xuezhen,LIU Jinbao,XU Bo,LI Gang
关键字: 骨关节炎;乌头汤;网络药理学;作用机制;中药系统药理学数据库及分析平台
KEYWORDS: Osteoarthritis; Wutou decoction; Network pharmacology; Mechanism; TCMSP
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