摘要
目的 基于网络药理学和分子对接技术探讨补中益气汤治疗慢性心力衰竭(CHF)的作用机制.方法 运用TCMSP、TCM-MESH、ETCM筛选补中益气汤的主要活性成分,通过Genecards、OMIM、Disgenet、TTD数据库获取CHF相关靶点.构建中药-疾病-有效成分-靶点网络,筛选中药核心成分.构建补中益气汤-CHF预测靶点的蛋白互作关系,筛选出核心靶点并进行GO和KEGG富集分析以及分子对接.结果 共获得135个活性成分,200个药物靶点,1 792个CHF靶点,104个交集基因.中药核心成分为槲皮素、山奈酚、柚皮苷、川陈皮素.核心靶点为AKT1、TNF、IL-6、IL-1β.GO分析主要富集于对激素的反应、细胞对细胞因子刺激的反应、激酶结合蛋白、蛋白质同源二聚化活性、脂筏、质膜蛋白复合物等.KEGG主要通路为癌症的信号转导通路、脂质和动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路.分子对接结果显示核心成分与核心靶点蛋白结合良好.结论 补中益气汤治疗慢性心力衰竭的作用机制,可能与其4个核心成分作用于AKT1、TNF、IL-6、IL-1β核心靶点,调控多个通路,起到抑制炎症、调节糖脂代谢和免疫反应等作用有关.
Abstract
Aim To explore mechanisms of Buzhongyiqi decoction in the treatment of chronic heart failure(CHF)based on network pharmacology and molecular docking techniques.Methods The main active ingredients of Buzhongyiqi decoction were i-dentified by using the TCMSP,TCM-MESH,and ETCM databases.CHF-related targets were obtained from GeneCards,OMIM,Dis-GeNET,and TTD databases.A traditional Chinese medicine-disease-effective ingredient-target network was constructed to identify the core components of the traditional Chinese medicine.The protein-protein interaction network between Buzhongyiqi decoction and CHF prediction targets was established to allow screening for the core targets.GO and KEGG enrichment analyses were performed on the key targets,and molecular docking studies were conducted.Results A total of 135 active ingredients,200 drug targets,1 792 CHF-related targets,and 104 intersecting genes were identified.The core components included quercetin,kaempferol,naring-in,and nobiletin.The core targets identified were AKT1,TNF,IL-6,and IL-1 β.GO analysis mainly included the response to hormones,the response of cells to cytokine stimulation,kinase binding proteins,protein homodimerization activity,lipid rafts,plasma membrane protein complexes,etc.The involved KEGG pathways primarily included cancer signaling pathways,lipid metabolism and atherosclerosis,and AGE-RAGE signaling pathways in diabetic complications.Molecular docking results indicated favorable binding interactions between the core ingredients and core target proteins.Conclusion The therapeutic mechanisms of Buzhongyiqi decoc-tion in treating chronic heart failure may involve its core components to target AKT1,TNF,IL-6,and IL-1 β,thereby regulating multi-ple pathways and inhibiting inflammation,glucose and lipid metabolism,and immune response.
基金项目
中国中医科学院眼科医院高水平中医医院建设项目(GSP3-07)
维普
万方数据