Institute of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China.
College of Pharmacy, Guilin Medical University, Guilin 541004, China.
Curr Pharm Des. 2024;30(36):2896-2910. doi: 10.2174/0113816128312242240722080551.
Diabetic cardiomyopathy (DCM) is a common diabetes complication with limited medications. Gegen Qinlian decoction (GQD) has been used in the treatment of diabetes and its related complications in China for several decades.
In this study, network pharmacology was employed to predict the active ingredients, key targets, and pathways involved in the treatment of DCM by GQD and to validate it by animal experiments.
The active ingredients of GQD were retrieved from TCMSP and published literature. DCM-related gene targets were searched in Drugbank, Genecards, Disgenet, and OMIM disease databases. Protein-protein interaction networks were constructed using the STRING database and Cytoscape. GO analysis and KEGG pathway enrichment analysis were performed using the Metascape platform. Moreover, a diabetic mouse model was established to evaluate the therapeutic effects of GQD by measuring serum biochemical markers and inflammation levels. Finally, the expression of predicted key target genes was determined using real-time quantitative PCR.
A total of 129 active ingredients were screened from GQD. Moreover, 146 intersecting genes related to DCM were obtained, with key targets, including AKT1, TNF, IL6, and VEGFA. Lipid and atherosclerosis, AGE-RAGE, PI3K-AKT, and MAPK pathways were identified. Blood glucose control, decreased inflammatory factors, and serum CK-MB levels were restored after GQD intervention, and the same occurred with the expressions of PPAR-γ, AKT1, APOB, and GSK3B genes.
Quercetin, kaempferol, wogonin, 7-methoxy-2-methyl isoflavone, and formononetin may exert major therapeutic effects by regulating key factors, such as AKT1, APOB, and GSK3B, in the inflammatory reaction, glycolipid oxidation, and glycogen synthesis related signaling pathways.
糖尿病心肌病（DCM）是一种常见的糖尿病并发症，治疗药物有限。葛根芩连汤（GQD）在中国已被用于治疗糖尿病及其相关并发症数十年。
本研究采用网络药理学方法预测 GQD 治疗 DCM 的活性成分、关键靶点和作用通路，并通过动物实验进行验证。
从 TCMSP 和已发表文献中检索 GQD 的活性成分。在 Drugbank、Genecards、Disgenet 和 OMIM 疾病数据库中搜索 DCM 相关基因靶点。使用 STRING 数据库和 Cytoscape 构建蛋白质-蛋白质相互作用网络。使用 Metascape 平台进行 GO 分析和 KEGG 通路富集分析。此外，通过测量血清生化标志物和炎症水平，建立糖尿病小鼠模型来评估 GQD 的治疗效果。最后，使用实时定量 PCR 测定预测关键靶基因的表达。
从 GQD 中筛选出 129 种活性成分。此外，获得了 146 个与 DCM 相关的交集基因，关键靶点包括 AKT1、TNF、IL6 和 VEGFA。鉴定出脂质和动脉粥样硬化、AGE-RAGE、PI3K-AKT 和 MAPK 通路。GQD 干预后血糖得到控制，炎症因子和血清 CK-MB 水平降低，同时 PPAR-γ、AKT1、APOB 和 GSK3B 基因的表达也发生了同样的变化。
槲皮素、山奈酚、白杨素、7-甲氧基-2-甲基异黄酮和芒柄花素可能通过调节 AKT1、APOB 和 GSK3B 等关键因子，在炎症反应、糖脂氧化和糖原合成相关信号通路中发挥主要治疗作用。
