基于网络药理学探讨生脉散治疗糖尿病心肌病的作用机制

Exploration on the Mechanism of Shengmai Powder in Treating Diabetic Cardiomyopathy Based on Network Pharmacology

目的 利用网络药理学方法探讨生脉散治疗糖尿病心肌病(DCM)的物质基础及作用机制。方法 通过TCMSP、BATMAN-TCM数据库、TCMID数据库、UniProt数据库获取生脉散有效成分及靶点;检索GeneCards、OMIM、PharmGKB、DrugBank数据库获得DCM相关靶点。两者取交集得到生脉散与DCM的共同靶点,采用Cytoscape3.8.0软件构建“药物成分-疾病靶点”网络,使用STRING数据库构建蛋白质-蛋白质相互作用(PPI)关系并绘制PPI网络,将PPI网络导入Cytoscape3.8.0进行拓扑结构分析,筛选核心靶点,采用R4.2.0软件进行GO功能和KEGG通路富集分析。结果 得到生脉散52个有效成分,包括N-反式-阿魏酰酪胺、山柰酚、红门兰醇、鲁斯可皂苷元、甲基麦冬黄烷酮B、甲基麦冬黄烷酮A、麦冬二氢高异黄酮A、麦冬二氢高异黄酮E、β-谷甾醇、豆甾醇等;获得195个生脉散治疗DCM相关的共同靶点,核心靶点包括STAT3、JUN、AKT1、RELA、MAPK14等。GO功能富集分析得到生物过程2 348个、细胞组分74个、分子功能197个,主要涉及对外来生物刺激的反应、衰老、细胞对非生物刺激的反应等;KEGG通路富集分析得到177条相关信号通路,包括脂质和动脉粥样硬化、流体剪切应力与动脉粥样硬化、AGE-RAGE信号通路、IL-17信号通路、PI3K-Akt信号通路等。结论 生脉散通过山柰酚、β-谷甾醇、豆甾醇及甲基麦冬黄烷酮B等高异黄酮类化合物,作用于STAT3、AKT1、MAPK14等靶点,介导AGE-RAGE信号通路、IL-17信号通路、PI3K-Akt信号通路等,发挥调节炎症、氧化应激、心肌纤维化等作用,从而防治DCM。

Objective To explore the material basis and mechanism of Shengmai Powder in the treatment of diabetic cardiomyopathy(DCM)using the network pharmacology.Methods The effective components and targets of Shengmai Powder were obtained from TCMSP database,BATMAN-TCM database,TCMID database and UniProt database;the DCM related targets were obtained from GeneCards,OMIM,PharmGKB and DrugBank databases.The common targets of Shengmai Powder and DCM were obtained by intersection of the two.A drug component-disease target network was constructed with Cytoscape 3.8.0 software,and the protein-protein interaction(PPI)relationship was constructed using STRING database, and the PPI network diagram was drawn. The PPI network diagram was imported into Cytoscape 3.8.0 for topology analysis, and the core targets were screened out. R 4.2.0 software was used for GO function and KEGG pathway enrichment analysis. Results A total of 52 effective components of Shengmai Powder were obtained, including N-trans-feruloyltyramine, kaempferol, orchinol, ruscogenin, methyl ophiopogonanone B, methyl ophiopogonanone A, ophiopogonanone A, ophiopogonanone E, β -sitosterol, and Stigmasterol. A total of 195 common targets related to the treatment of DCM were identified for Shengmai Powder. The core targets included STAT3, JUN, AKT1, RELA, MAPK14, and others. GO analysis revealed 2 348 biological processes, 74 cellular components, and 197 molecular functions. The main processes involved responses to external biological stimuli, aging, and responses of cells to non-biological stimuli. KEGG analysis identified 177 related signaling pathways, including lipid and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. Conclusion Shengmai Powder can target STAT3, AKT1 and MAPK14 through high flavonoid of kaempferol, β -sitosterol, stigmasterol and methyl ophiopogonanone B, and AGE-RAGE signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway are mediated to regulate inflammation, oxidative stress and myocardial fibrosis to prevent and treat DCM.