青风藤治疗骨性关节炎药效物质基础多靶导向作用的计算机模拟研究

Computational Simulation of Multi-target Research on the Material Basis of Caulis sinomenii in Treating Osteoarthritis

目的探讨青风藤治疗骨性关节炎(osteoarthritis,OA)的药效物质基础,并对青风藤多靶导向作用做出药效学阐释。方法 (1)构建青风藤化学成分分子数据库,应用分子对接探讨其与OA重要靶标的相互作用;(2)构建青风藤所含分子配体-靶作用网络及DrugBank药物库中有关OA的药物分子配体-靶作用网络,分析其网络特征,阐明青风藤治疗OA作用机制和特点。结果青风藤中共有14个化学成分分子与2个及2个以上靶点相互作用,其中6个化学成分分子对4个及4个以上靶点有作用效应。青风藤分子配体-靶作用网络与药物分子配体-靶作用网络的轮廓和特征相似。结论青风藤存在多成分、多靶导向效应,且部分成分存在多靶导向效应,为青风藤治疗OA的药效学分子机制提供了解释,同时也为寻找治疗OA的新型药物提供一定的参考和借鉴。

Objective To explore the material basis of Caulis sinomenii（CS） in treating osteoarthritis（OA） ,and to give a pharmacodynamic illustration for the multi-targeting therapeutics of CS.Methods The computational methods,consisting of molecular docking and biological network were carried out to search the database targeting twelve important OA related enzymes：ASAMTS4,ASAMTS5,MMP-1,MMP-3,MMP-13,MMP-8,MMP-2,COX-2,COX-1,IL-1β,TNF-α,iNOS,and map the ligand-target interaction networks about molecules from CS and DrugBank.After that,an aggregate analysis was performed to analyze the mechanisms of compositions in CS.Results Totally 14 had good interaction in all molecules in database with two or more than two of the OA correlated enzymes,and 6 molecules had interaction with four or more enzymes.Moreover,both herb ligand-target interaction network and drug ligand-target interaction network were similar in the interaction profiles and network features,which revealed multi-drugs effects in CS.Conclusions There were a lot of multi-target molecules in CS,providing pharmacodynamic illustrations for the multi-target therapeutics of Chinese medicine.Meanwhile,they supplied certain reference and inspiration for finding out new drugs for OA therapy.