“独活-桑寄生”药对治疗膝骨性关节炎的药理学及分子对接分析

Pharmacology and Molecular Docking Analysis of"Duhuo-Mulberry Parasitism"in the Treatment of Knee Osteoarthritis

目的:采用整合药理学平台分析“独活-桑寄生”治疗膝骨性关节炎(KOA)的作用机制。方法:通过药理学数据库查找出“独活-桑寄生”药对的活性成分及作用靶点,并从数据库平台查找出KOA的疾病靶点,利用软件分析出药对和疾病的交集靶点及其相应的活性成分,构建药物-成分-KOA网络图。基于交集靶点构建蛋白互作网络(PPI),应用平台及软件进行GO和KEGG富集分析,并采用分子对接技术进行验证。结果:筛选出“独活-桑寄生”有效成分11个,作用靶点151个,KOA靶点2261个,分析得到药物-疾病的交集靶点94个,根据度值排名靠前的为TNF、ILB、AKT1、TP53、MMP9、CASP3等;通过GO分析发现,涉及的范围包括脂多糖、细菌源性分子反应、氧化应激等;KEGG富集分析表明主要涉及AGE-RAGE、TNF和IL-17等信号通路。结论:“独活-桑寄生”药对KOA的治疗作用可能主要通过调节IL6、VEGFA、CCL2等靶点,涉及的通路主要为AGE-RAGE、TNF、IL-17、NF-κB等。

Objective:To analyze the mechanism of"Duhuo-Mulberry Parasitism"in the treatment of knee osteoarthritis(KOA).Methods:The active components and action targets of"Duhuo-Mulberry Parasitic"drug pair were found out through the pharmaceutical database,and the disease targets of KOA were found out from the database platform.The intersection targets of drug pairs and diseases and their corresponding active components were analyzed by software,and the drug-component-KOA network was constructed.The protein-protein interaction network(PPI)was constructed based on the intersection target,the platform and software were used for GO and KEGG enrichment analysis,and subsequently verified by using molecular docking technology.Results:11 Active components,151 action targets and 2261 KOA targets were screened out from"Duhuo-Mulberry Parasitism".According to the analysis,94 drug-disease intersection targets were obtained,and the top ones were TNF,ILB,AKT1,TP53,MMP9,CASP3,etc;through GO analysis,it was found that the scope involved includes lipopolysaccharide,bacterial derived molecular reaction,oxidative stress,etc.KEGG enrichment analysis showed that it mainly involved AGE-RAGE,TNF and IL-17 signaling pathways.Conclusion:The therapeutic effect of"Duhuo-Mulberry Parasitism"on KOA may be mainly through regulating targets such as IL6,VEGFA and CCL2,and the pathways involved are mainly AGE-RAGE,TNF,IL-17 and NF-κB,etc.