基于网络药理学和分子对接技术研究黄芪-赤芍治疗COPD的作用机制

Study of the Mechanism of Radix Astragali seu Hedysari-Radix Paeoniae Rubra in the Treatment of COPD Based on Network Pharmacology and Molecular Docking

目的基于网络药理学和分子对接技术探究黄芪-赤芍配伍对治疗慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的作用机制。方法利用TCMSP,Pharmmaper数据库,筛选黄芪-赤芍治疗COPD的活性成分和潜在靶点;结合Genecards数据库挖掘的COPD相关靶点,对黄芪-赤芍药对与COPD靶点进行PPI网络构建,交互处理得到黄芪-赤芍药对治疗COPD的关键靶点,并进行GO分析和KEGG通路富集分析;并采用分子对接技术将主要活性成分与TNF-α(肿瘤坏死因子),IL-6(白细胞介素6)等进行分子对接;最后利用A549炎症细胞与人脐静脉内皮细胞缺氧损伤模型进行体外细胞实验对结果加以验证。结果黄芪-赤芍药对中44个有效成分作用于COPD,核心成分为:槲皮素、山奈酚、丁子香萜、芍药苷、(2R,3R)-4-methoxyl-distylin、二氢异黄酮;黄芪-赤芍药对通过IL6、PTGS2、TNF等113个靶蛋白,调控Ras、PI3KAkt、IL-17等多条信号通路治疗COPD,且分子对接结果显示槲皮素、山奈酚、丁子香萜、芍药苷与IL-6、PTGS2、TNF大分子蛋白有良好的结合性,体外细胞试验证实,槲皮素与山奈酚均能减少IL-8,MMP-9炎症因子的分泌,具有不同程度的抗炎效果;芍药苷有明显的扩血管、抗血栓之效。结论黄芪-赤芍药对治疗COPD具有多成分、多靶点、多通路、整体调节的作用特点。初步揭示了黄芪-赤芍药对通过抑制炎症反应、调节上皮细胞生长增强保护屏障等预测出黄芪-赤芍药对治疗COPD的潜在作用机制,以期为其活性成分的药效物质基础提供理论研究和思路。

Objective To explore the mechanism of Radix Astragali seu Hedysari-Radix Paeoniae Rubra in the treatment of chronic obstructive pulmonary disease(COPD)based on network pharmacology and molecular docking.Method TCMSP,Pharmmaper database was used to screen the active ingredients and potential targets of Radix Astragali seu Hedysari-Radix Paeoniae Rubra for the treatment of COPD;combined with COPD-related targets mined from Genecards database,PPI network construction was performed for Radix Astragali seu Hedysari-Radix Paeoniae Rubra and COPD targets,and cross-processing was performed to obtain the key targets of Radix Astragali seu HedysariRadix Paeoniae Rubra for the treatment of COPD,and GO analysis and Finally,the results were validated by in vitro cellular experiments using A549 inflammatory cells and human umbilical vein endothelial cells hypoxic injury model.Results The 44 active ingredients in Radix Astragali seu Hedysari-Radix Paeoniae Rubra act on COPD,the core components are:quercetin,kaempferol,eugenol,paeoniflorin,(2 R,3 R)-4-methoxyl-distylin,dihydroisoflavone;Astragalus-erythrina pair regulates Ras,PI3 KAkt,IL-17 through 113 target proteins such as IL6,PTGS2,TNF and other signaling pathways for COPD,and the molecular docking results showed that quercetin,kaempferol,butyrospermum terpene,and paeoniflorin had good binding to IL-6,PTGS2,TNF macromolecular proteins,and in vitro cellular assays confirmed that both quercetin and kaempferol could reduce the secretion of IL-8,MMP-9 inflammatory factors,with different degrees of anti-inflammatory effects;paeoniflorin had significant vasodilating and antithrombotic effect.Conclusion Radix Astragali seu Hedysari-Radix Paeoniae Rubra exhibits multi-component,multi-target,multipathway and overall modulating effects on the treatment of COPD.The potential mechanism of Radix Astragali seu Hedysari-Radix Paeoniae Rubra on the treatment of COPD through inhibition of inflammatory response and regulation of epithelial cell growth to enhance the protective barrier was preliminarily revealed in order to provide theoretical studies and ideas for the pharmacodynamic material basis of its active ingredients.