羌活-独活治疗膝骨关节炎的作用机制

The mechanism of action of notopterygium incisum-angelica pubescensin treating KOA

目的基于网络药理学筛选羌活-独活的主要活性化学成分,查找其对应靶点,构建羌活-独活治疗膝骨关节炎(knee osteoarthritis,KOA)潜在靶点网络,探讨羌活-独活治疗膝骨关节炎的作用机制。方法在中药系统药理数据库(TCMSP)中通过口服生物利用度和药物相似性筛选羌活-独活的主要活性成分;再通过GeneCard、OMIM、PharmGkb、Therapeutic Targets和DrugBank数据库构建膝骨关节炎的靶标数据库;通过STRING数据库和Cytoscape 3.8.0构建潜在靶点及靶点间蛋白的相互关系;对核心靶点进行KEGG通路富集分析和GO生物学功能分析;通过Discovery Studio将羌活-独活的活性成分与KOA相关的前3个核心靶点进行分子对接。结果从羌活-独活中筛选出12个活性成分、16个防治膝骨关节炎的潜在靶点。网络药理学分析结果表明羌活-独活治疗膝骨关节炎的靶点主要涉及细胞凋亡、雌激素、P53、白细胞介素-17(IL-17)、糖基化终末产物及其受体(AGE-RAGE)等信号通路。分子对接显示羌活-独活活性成分与KOA相关的3个核心靶点均能较好对接。结论羌活-独活能够通过多成分、多通路、多靶点治疗膝骨关节炎,本研究为羌活-独活治疗膝骨关节炎提供了理论依据和新方向。

Objective To explore the main active chemical components of Notopterygium incisum-Angelica pubescens and obserive the mechanism of action in the treatment of knee osteoarthritis to find their corresponding targets Based on the network pharmacology.Methods The main active components in The Chinese medicinal systematic-pharmacology database(TCMSP)were screened by oral bioavailability and drug similarity.Furthermore,target databases for knee osteoarthritis were established through GeneCard,OMIM,PharmGkb,Therapeutic Targets and DrugBank databases.The potential targets and the interaction between the targets were constructed by using the STRING database and Cytoscape3.8.0.The Kyoto Encyclopedia of Genes and Genes(KEGG)pathway and gene ontology(GO)biological process enrichment analysis were performed on the core targets.In addition,we also conducted molecular docking for the first 3 KOA-related targets of the active ingredients of Notopterygium incisum-Angelica pubescens through Discovery Studio.Results 12 active components and 16 potential targets for the prevention and treatment of knee osteoarthritis were screened out from Notopterygium incisum-Angelica pubescens.The result of the network pharmacologic analysis showed that the targets of Notopterygium incisum-Angelica pubescens in the treatment of knee osteoarthritis were mainly involved in cell apoptosis,estrogen,P53,interleukin-17(IL-17),glycation end products and their receptor(AGE-RAGE)signaling pathways.Molecular docking showed that the first 3 targets of KOA could be well docked with the active components of KOA.Conclusion This study provides a theoretical basis and a new direction for the treatment of knee osteoarthritis by Notopterygium incisum-Angelica pubescens with multiple components,pathways and targets.