基于网络药理学与分子对接探讨山茱萸-菟丝子治疗认知障碍的作用机制

Exploring on the Mechanism of Corni Fructus-Cuscutae Semen on Cognitive Impairment Based on Network Pharmacology and Molecular Docking

目的 利用网络药理学和分子对接方法探讨山茱萸-菟丝子治疗认知障碍的潜在作用机制。方法 利用TCMSP筛选山茱萸、菟丝子活性成分,并预测潜在靶点,从UniProt数据库获得药物成分对应靶点,通过TTD、GeneCards和OMIM数据库获取认知障碍相关靶点,利用R4.2.2软件获取山茱萸-菟丝子与认知障碍的共同靶点。利用Cytoscape3.7.2软件构建“药物-活性成分-靶点”网络,通过STRING11.5数据库构建共有靶点蛋白相互作用网络,利用R4.2.2软件进行GO功能及KEGG通路富集分析,利用AutoDock1.5.6、PyMoL2.4.0软件进行分子对接验证。结果 经过筛选共得到30个药物活性成分,184个药物-疾病交集靶点,通过GO功能和KEGG通路富集分析得到2 678个GO条目和179条信号通路。共同靶点的通路富集分析显示主要与PI3K-Akt、HIF-1α/VEGF等信号通路相关,分子对接结果显示,认知障碍核心靶点与山茱萸-菟丝子主要成分亲和力较好,可能有效自由结合。结论 山茱萸-菟丝子中槲皮素、山柰酚、β-谷甾醇、异鼠李素、豆甾醇、四氢鸭脚木碱等成分可能通过抗氧化应激、抗炎及免疫调节、糖脂调节等作用治疗认知障碍。

Objective To explore the potential mechanism of Corni Fructus-Cuscutae Semen in the treatment of cognitive impairment using network pharmacology and molecular docking technique.Methods The active components of Corni Fructus and Cuscutae Semen were obtained from TCMSP database,and the potential targets were predicted.The targets of drug components were obtained from the UniProt database.The targets of cognitive impairment were obtained from TTD,GeneCards,OMIM databases,and the common targets of the medicinal pair and cognitive impairment were analyzed with R 4.2.2 software.Cytoscape 3.7.2 software was used to construct a network of “drug-active components-target”. The protein-protein interaction network of common target was constructed through STRING 11.5 database, perform GO and KEGG pathway enrichment analysis using R 4.2.2 software. The molecular docking analyses were performed using AutoDock 1.5.6 and PyMoL 2.4.0 software. Results A total of 30 drug active components and 184 drug-disease intersection genes were obtained after screening. Totally 2 678 GO items and 179 signaling pathways were obtained through GO and KEGG enrichment analysis. Pathway enrichment analysis of common targets showed that they were mainly related to PI3K-Akt and HIF-1α/ VEGF signaling pathways. The results of molecular docking showed that the core target of cognitive impairment had good affinity with the main components of Corni Fructus-Cuscutae Semen, which maybe bind freely and effectively. Conclusion Quercetin, kaempferol, β-sitosterol, isorhamnetin, stigosterol, tetrahydroalstonine and other components in the Corni Fructus-Cuscutae Semen maybe play a role in the treatment of cognitive impairment through anti oxidative stress, anti-inflammation, immune regulation, glucose and lipid regulation.