基于化学生物信息学探究大泻肺汤“体-用-化”功能配伍治疗慢性阻塞性肺疾病的活性成分

Using chemo-bio informatics to explore the active ingredients of“Ti-Yong-Hua”functional compatibility of Daxiefei Decoction in the treatment of COPD

目的基于敦煌《辅行诀五脏用药法要》(简称《辅行诀》)“体-用-化”辨证理论,运用化学生物信息学方法探究大泻肺汤“体-用-化”功能配伍治疗慢性阻塞性肺疾病(COPD)的活性成分。方法基于“体-用-化”辨证理论,对大泻肺汤各药味进行分组。通过网络药理学方法探究各组治疗COPD的关键靶点及关键成分,采用基于分子对接的虚拟筛选方法对大泻肺汤全方中能够与成药性靶点磷酸二酯酶4有效结合来发挥治疗COPD的成分进行筛选。结果肺脏各组具有通过靶向RAC-α-丝氨酸/苏氨酸蛋白激酶、丝裂原活化蛋白激酶等靶点,调控磷脂酰肌醇-3-激酶等信号通路发挥改善机体呼吸困难的潜在功能;肺的子脏-肾脏各组可通过靶向基质金属蛋白酶2、表皮生长因子受体2等靶点,调控核因子κB等信号通路,从而发挥辅助减轻COPD患者肺部炎症、调节机体呼吸的作用。分子对接结果发现代表性化合物甘草利酮、Phaseol、甘草吡喃香豆素和Glyzaglabrin可能是大泻肺汤防治COPD的潜在活性成分。结论本研究利用化学生物信息学方法对敦煌大泻肺汤进行“体-用-化”功能配伍分组治疗COPD潜在起效的成分及作用机制进行挖掘,为敦煌大泻肺汤的临床推广应用奠定了基础。

Objective Based on the theory of syndrome differentiation and treatment of“Ti-Yong-Hua”in books of“Fu Xing Jue Visceral to Drug Law”,chemo-bio informatics method was used to explore the active ingredients of“Ti-Yong-Hua”functional compatibility of Daxiefei Decoction in the treatment of chronic obstructive pulmonary disease(COPD).Methods Daxiefei Decoction was divided into groups according to the theory of“Fu Xing Jue Visceral to Drug Law”.The key targets and key components in the treatment of COPD in the“Ti-Yong-Hua”groups of Daxiefei Decoction were explored via network pharmacological methods,and molecular docking verification was performed on the key targets.Moreover,molecular docking was used for virtual screening of the components in Daxiefei Decoction,which could be effectively combined with the druggable target phosphodiesterase 4 to facilitate the treatment of COPD.Results The Fei groups had the potential function of improving dyspnea by targeting RAC-alpha serine/threonine-protein kinase,mitogen-activated protein kinase and regulating phosphatidylinositol 3-kinase and other signaling pathways.By targeting matrix metalloproteinases,epidermal growth factor receptor 2 and other targets,Shen groups had regulated nuclear factor kappa-B and other signaling pathways,thus playing a role in assisting the reduction of pulmonary inflammation and regulating respiration in COPD patients.It was found that Licoricone,Phaseol,Licopyranocoumarin,Glyzaglabrin might be the potential active ingredients of Daxiefei Decoction for the prevention and treatment of COPD.Conclusion In this study,the chemo-bio informatics method was used to explore the potential components and mechanism of the“Ti-Yong-Hua”model of Daxiefi Decoction in the treatment of COPD,which might lay a foundation for the clinical application of Dunhuang Daxiefei Decoction.