基于网络药理学与分子对接探讨麻黄对银屑病的作用机制

The action mechanism of Mahuang in the treatment of psoriasis based on network pharmacology and molecular docking

目的:基于网络药理学及分子对接技术,预测麻黄治疗银屑病的潜在作用靶点及相关通路。方法:利用中药系统药理学数据库与分析平台(TCMSP)筛选麻黄活性成分及对应靶点,在GeneCards、OMIM、DrugBank等数据库检索银屑病疾病靶点信息,取麻黄与银屑病的交集靶点,并构建蛋白质-蛋白质相互作用网络。通过DAVID平台进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,使用AutoDock软件进行分子对接分析。结果:麻黄治疗银屑病主要成分为豆甾醇、β-谷甾醇、香叶木素、柳穿鱼黄素以及芫花素,麻黄与银屑病共有27个交集靶点,核心靶点包括半胱氨酸天冬氨酸蛋白酶3(Caspase 3,CASP3)、前列腺素氧化环化酶2(Prostaglandin-Endoperoxide Synthase 2,PTGS2)、一氧化氮合酶2(Nitric Oxide Synthase 2,NOS2)、溶质载体家族6成员4(Solute Carrier Family 6 Member 4,SLC6A4)、乙酰胆碱酯酶(Acetylcholinesterase,ACHE),潜在靶点富集在胆碱能突触、5-羟色胺突触、晚期糖基化终末产物(Advanced Glycation Endproduct,AGE)与其受体(Receptor for Advanced Glycation End Products,RAGE)、肿瘤蛋白p53等信号通路上。分子对接结果表明麻黄主要成分与核心靶点拥有较高亲和力。结论:麻黄可能通过促进角质形成细胞凋亡,调控核因子-κB(Nuclear Factor-κB,NF-κB)、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(Akt)、信号转导因子和转录激活因子(Signal Transducer and Activator of Transcription,STAT)等炎症通路,减少肿瘤坏死因子(Tumor Necrosis Factor,TNF)-α、白细胞介素(Interleukin,IL)-1β、IL-6等炎症因子的释放,从而改善银屑病皮损。

Objective:Based on network pharmacology and molecular docking technology,the potential targets and related pathways of Mahuang(Herba Ephedrae)in the treatment of psoriasis were predicted.Methods:The active constituents and corresponding targets of Mahuang were screened by TCMSP database.Psoriasis target information was retrieved from GeneCards,OMIM,DrugBank and other databases.The intersection target of Mahuang and psoriasis was selected and the protein-protein interaction network was constructed.GO analysis and KEGG analysis were performed through DAVID platform.Molecular docking analysis was performed using AutoDock software.Results:The main components of Mahuang in the treatment of psoriasis are stigasterol,β-sitosterol,geranolin,salicin and genkyugenin.Mahuang and psoriasis have a total of 27 intersection targets,and the core targets include CASP3,PTGS2,NOS2,SLC6A4,ACHE.Potential targets are concentrated in cholinergic synapses,5-hydroxytrypsin synapses,AGE-RAGE,TP53 and other signaling pathways.The results of molecular docking showed that the main components of Mahuang had high affinity with the core target.Conclusion:Mahuang may improve psoriatic lesions by promoting keratinocyte apoptosis,regulating inflammatory pathways such as NF-κB,PI3K/Akt and STAT3,and reducing the release of TNF-α,IL-1βand IL-6.