基于网络药理学分析绞股蓝治疗糖尿病性心肌病的作用机制  

The action mechanism of Jiaogulan in the treatment of diabetic cardiomyopathy based on network pharmacology

作　　者：冯雪 彭立 FENG Xue

机构地区：[1]贵州中医药大学,贵州贵阳550025

出　　处：《中医临床研究》2024年第28期1-8,共8页Clinical Journal Of Chinese Medicine

基　　金：国家自然科学基金委员会地区科学基金项目(81960857)。

摘　　要：目的:利用网络药理学方法探讨绞股蓝治疗糖尿病性心肌病(Diabetic Cardiomyopathy,DCM)的作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)、PharmMapper、Genecards数据库中获取“绞股蓝”活性成分及其靶点、疾病靶点,使用Cytoscape绘制药物活性成分-疾病交集靶点网络图,利用STRING平台构建交集靶点的蛋白质-蛋白质相互作用网络图,通过OmicShare Tools平台进行基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。利用分子对接软件Autodock对核心靶点和主要活性成分进行分子对接验证。结果:筛选得到24个绞股蓝活性成分,其中与DCM的交集靶点50个。人参皂苷F2、绞股蓝皂苷XII、绞股蓝皂苷XXXII、绞股蓝皂苷XXXV_qt、绞股蓝皂苷LXXIV等是绞股蓝治疗DCM的主要活性成分,蛋白质-蛋白质相互作用网络提示白蛋白(Albumin,ALB)、雌激素受体1(Estrogen Receptor1,ESR1)、半胱氨酸蛋白酶3(Caspase 3,CASP3)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、热休克蛋白90α家族A类成员1(Heat Shock Protein 90 Alpha Family Class A Member 1,HSP90AA1)、过氧化物酶体增殖物激活受体γ(Peroxisome Proliferator Activated Receptor Gamma,PPARG)等可能是绞股蓝治疗DCM的核心靶点。KEGG富集分析显示主要信号通路有白细胞介素(Interleukin,IL)-17信号通路、脂质与动脉粥样硬化、糖尿病并发症中的晚期糖基化终末产物(Advanced Glycation End Product,AGE)-晚期糖基化终末产物受体(Advanced Glycation End Product Receptor,RAGE)信号通路、幽门螺杆菌感染中的上皮细胞信号传导等。分子对接验证提示核心靶点和主要成分之间具有优秀的结合活性。结论:绞股蓝通过多成分、多靶点、多通路以发挥降糖、抗炎、改善能量代谢、抗氧化应激、改善内分泌抵抗等生理学功能,从而治疗DCM。Objective:To investigate the action mechanism of Jiaogulan(Herba Gynostemmae Pentaphylli)in the treatment of diabetic cardiomyopathy based on network pharmacology.Methods:The active ingredients and targets of Jiaogulan and disease targets were obtained from TCMSP,PharmMapper and Genecards databases.Cytoscape was used to draw the network diagram of the active ingredient-disease intersetion target.STRING platform was used to construct the protein-protein interaction network of intersecting targets.GO and KEGG enrichment analyses were performed on OmicShare Tools platform,and molecular docking software Autodock was used to validate the molecular docking between the core targets and main active ingredients.Results:Twenty-four active ingredients of Jiaogulan were screened,among which 50 targets were intersected with diabetic cardiomyopathy.Ginsenoside F2,gibberellin XII,gibberellin XXXII,gibberellin XXXV_qt,and gibberellin LXXIV were the main active ingredients of Jiaogulan in the treatment of diabetic cardiomyopathy.The protein-protein interaction network suggested that ALB,ESR1,CASP3,EGFR,HSP90AA1,and PPARG might be the core targets of Jiaogulan in the treatment of diabetic cardiomyopathy.KEGG enrichment analysis showed that the signaling pathways involved were mainly IL-17 signaling pathway,lipids and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,and epithelial cell signaling in Helicobacter pylori infection.Molecular docking result verified excellent binding activity between the core target and the main components.Conclusion:Jiaogulan works through multi-component,multi-target,and multi-pathway in order to exert physiological functions such as hypoglycemia,anti-inflammation,improvement of energy metabolism,anti-oxidative stress,and improvement of endocrine resistance,and thus treat diabetic cardiomyopathy.

关 键 词：绞股蓝 网络药理学 糖尿病性心肌病 

分 类 号：R542[医药卫生—心血管疾病]