摘要
目的:利用网络药理学平台整合分析牛膝-杜仲-桑寄生治疗膝骨关节炎(KOA)的分子机制,为药组的使用提供理论依据。方法:通过TCMSP平台筛选药组有效成分及靶点,与KOA靶点取交集制作韦恩图,构建蛋白质-蛋白质相互作用(PPI)网络图,筛选关键成分和核心基因,对核心靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果:筛选出药组有效成分41种,作用靶点239个;主要有槲皮素、山柰酚、β-谷甾醇、黄芩素、汉黄芩素、β-胡萝卜素等关键成分;磷酸激酶B1(AKT1)、半胱氨酸蛋白酶3(CASP3)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、血管内皮生长因子(VEGF)等核心基因。关键信号通路有晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)通路、TNF通路、脂肪与动脉粥样硬化通路、磷脂酰肌醇3-激酶/磷酸激酶B(PI3K/Akt)通路等,分子对接结果显示活性成分与核心基因结合能力较强。结论:牛膝-杜仲-桑寄生药组可以通过多靶点、多通路发挥抗炎、抗氧化、调控细胞凋亡及稳定关节内环境的作用,达到治疗膝骨关节炎的目的。
Objective:To investigate the molecular mechanism of Radix Achyranthis Bidentatae-Eucommia ulmoides-Herba Taxilli in the treatment of knee osteoarthritis(KOA)based on network pharmacology platforms,and to provide a theoretical basis for the use of this drug combination.Methods:TCMSP platform was used to obtain the effective constituents and targets of the drug combination,which were intersected with the targets of KOA by Venn diagram.A protein-protein interaction network was constructed to obtain the key components and the core genes,and gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for the core targets.Results:A total of 41 effective constituents and 239 action targets were obtained for the drug combination,with the key components of quercetin,kaempferol,beta-sitosterol,baicalein,wogonin,andβ-carotene,and the core genes included AKT1,CASP3,IL-6,TNF,and VEGF.Key signaling pathways included the AGE-RAGE pathway,the TNF pathway,the lipid and atherosclerosis pathway,and the PI3K/Akt pathway,and molecular docking showed good binding activity between the active components and the core genes.Conclusion:The drug combination of Radix Achyranthis Bidentatae-Eucommia ulmoides-Herba Taxilli can exert the anti-inflammatory and antioxidant effect,regulate cell apoptosis,and stabilize articular internal environment via multiple targets and pathways,thereby exerting a therapeutic effect on KOA.
作者
范伟
费熙
李小平
唐光平
FAN Wei;FEI Xi;LI Xiaoping;TANG Guangping(Hubei University of Chinese Medicine,Wuhan 430061,Hubei,China;Hospital of Traditional Chinese Medicine Affiliated to Hubei University of Chinese Medicine/Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430050,Hubei,China)
出处
《湖南中医杂志》
2023年第12期157-164,共8页
Hunan Journal of Traditional Chinese Medicine
关键词
膝骨关节炎
牛膝
杜仲
桑寄生
网络药理学
knee osteoarthritis
Radix Achyranthis Bidentatae
Eucommia ulmoides
Herba Taxilli
network pharmacology
