六经头痛片治疗脑缺血作用机制的网络药理学和分子对接研究

Mechanism of Liujing Toutong Tablets in Treatment of Cerebral Ischemia Based on Network Pharmacology and Molecular Docking

目的利用网络药理学方法预测六经头痛片治疗脑缺血的核心成分和靶点,并通过分子对接初步验证。方法在TCMSP、CRD、HERB数据库查询六经头痛片9味组成药物的化学成分,在PubChem和Swiss ADME平台获取化学成分SMILES结构并进行标准化,利用化合物SMILES结构在SEA数据库进行靶点预测;在OMIM、Drugbank、CTD数据库获得脑缺血疾病靶点,利用Venny 2.0获得药物和疾病的共同靶点,把共同靶点放入STRING 11.5数据库进行PPI分析,利用Cytoscape 3.7.2绘制PPI网络以及六经头痛片治疗脑缺血“药物-化学成分-靶点-通路”网络图;利用AutoDock 1.5.6软件进行分子对接。结果共得到六经头痛片63个有效化学成分和200个作用靶点,药物和疾病共同靶点27个,筛选得到核心化学成分β-石竹烯(Beta-Caryophyllene,BCP)、6-去氢姜二酮(6-Dehydrogingerdione,6-DG)、薄荷酮(Menthone)、落叶松脂醇(Lariciresinol),以及关键靶点白介素-6(IL-6)、肿瘤坏死因子(TNF-α)、转录因子AP-1(Transcription factor AP-1,JUN)、半胱天冬酶3(Caspases3,CASP3)。结论六经头痛片中的β-石竹烯、6-去氢姜辣二酮、薄荷酮、落叶松脂醇可能通过作用于IL-6、TNF-α、JUN、CASP3从而发挥治疗脑缺血疾病的疗效。

Objective To predict the core components and targets of Liujing Toutong Tablets in the treatment of cerebral ischemia by network pharmacologyfollowed by preliminary verification through molecular docking.Methods The chemical components of ninedrugsin Liujing Toutong Tablets were retrievedfrom TCMSP,CRD,and HERB.The SMILES structures of chemical components were obtained and standardized on PubChem and Swiss ADME platforms,and targets were predicted by SMILES structures in SEA.The disease targets for cerebral ischemia were obtained from OMIM,Drugbank,and CTD,and common targets for the drug and the disease were obtained using Venny 2.0.The common targets were put into STRING 11.5 for PPI analysis.The PPI network and“drug-component-target-pathway”network of Liujing Toutong Tablets in the treatment of cerebral ischemia were plotted by Cytoscape 3.7.2.AutoDockwas used for molecular docking.Results Sixty-three active chemical components and 200 targets of Liujing Toutong Tablets were obtained,and there were 27 common targets of the drug and the disease.The core chemical components β-caryophyllene(BCP),6-dehydrogingerdione(6-DG),menthone,and lariciresinol,and key targets interleukin-6 (IL-6),tumor necrosis factor(TNF)-α,transcription factor AP-1(JUN),and Caspases3(CASP3)were screened out.Conclusion The components BCP,6-DG,menthone,and lariciresinol in Liujing Toutong Tablets may play a therapeutic effect on cerebral ischemia by acting on IL-6,TNF-α,JUN,and CASP3.