基于网络药理学和分子对接探讨藏麻黄挥发性成分对支气管炎的作用机制

麻黄(Ephedrae Herba)具有发汗散寒、宣肺平喘、利水消肿的功效。现代研究表明麻黄对治疗支气管、哮喘有疗效。藏麻黄(Ephedra saxatilis)为西藏特有的麻黄属植物,其根、茎具有特殊香气,且目前其挥发性成分未有报道。为评价挥发性成分对支气管炎作用,用气质联用仪测定分析藏麻黄根、茎挥发性成分,并结合网络药理学和分子对接方法分析挥发性成分治疗支气管炎的关键靶点。分析检测到67个挥发性化合物,茎中含有挥发性主要成分为2,3,5,6-四甲基吡嗪(10.92%)、Z-9-十五烯醇(9.15%)、二羟基苯乙酮(7.92%);根含有的挥发性主要成分为亚油酸(7.81%)、红没药醇(7.1%)、Z-9-十五烯醇(5.98%)。有34个挥发性成分能够作用32个支气管炎疾病靶点。蛋白互作网络分析预测IL6、TNF、PTGS2、CXCL8为藏麻黄挥发性成分治疗支气管可能的潜在靶点。这些靶点与挥发性成分丁子香酚、月桂酸、反式法尼醇、α-萜品醇、榄香醇和棕榈酸6种化合物靶点相互结合程度高,且分子对接效果好。本研究推测藏麻黄挥发性成分对支气管炎的治疗作用机制可能是通过抑菌作用参与炎症反应,并通过抑制TNF、IL-17、Toll样受体等炎症与免疫信号通路中IL6、TNF、PTGS2、CXCL8的表达,从而起到治疗支气管炎的作用。研究结果为挖掘藏麻黄挥发性成分中治疗支气管炎靶标分子及其产品开发提供重要参考依据。

Study on therapeutic mechanism of volatile components from Ephedra saxatilis in treating bronchitis based on network pharmacology and molecular docking

Ephedrae Herba can disperse cold,relieve asthma and reduce swelling.Ephedrae Herba has been used in herbal medicine to cure bronchial asthma.Ephedra saxatilis is one of the species of the Ephedra genus endemic to Tibet.Its roots and stems have a special aroma,but its volatile components have not been well studied.To reveal its volatile chemical constituents and its therapeutic mechanism for treating bronchitis,the volatile components in roots and stems of Ephedra saxatilis were studied using gas chromatography-mass spectrometry.The key targets of volatile components in the treatment of bronchitis were analyzed by network pharmacology and molecular docking.A total of 67 volatile compounds were identified by GC-MS.The main volatile components in stems were 2,3,5,6-tetramethyl-1,4-pyrazine(10.92%),pentadecenol(9.15%),2,2-dihydroxy-1-phenyl-ethanon(7.92%),and in roots were octadecadienoic acid(7.81%),bisabolone(7.1%),and pentadecenol(5.98%).A total of 34 volatile compounds acted on 32 targets associated with bronchitis.The target network analysis showed that IL6,TNF,PTGS2 and CXCL8 have high degrees of interaction,and so might be key targets of volatile components of E.saxatilis in the treatment of bronchitis.Six compounds,namely dodecanoic acid,trans-farnesol,α-terpineol,elemol,and hexadecanoic acid,were predicted to be potential binding compounds for treating bronchitis.Docking analysis showed that the six compounds have high binding interactions with IL6,TNF,PTGS2 and CXCL8.We predict the therapeutic mechanism of volatile components of E.saxatilis on bronchitis might be through the inflammatory response involving bacteriostasis and inhibition of the expression of IL6,TNF,PTGS2 and CXCL8 targets in inflammatory and immune signaling pathways such as TNF,IL-17 and Toll-like receptors.The research may provide important clues for finding molecular targets in treating bronchitis.