Active Ingredients and Mechanism of Gegen Qinlian Decoction in the Treatment of Diabetic Cardiomyopathy: A Network Pharmacology Study


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Abstract

Background: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.

Objective: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.

Methods: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.

Results: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.

Conclusion: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.

About the authors

Min Wang

Institute of Basic Medical Sciences, Guilin Medical University

Email: info@benthamscience.net

Yanbin Liang

College of Pharmacy, Guilin Medical University

Email: info@benthamscience.net

Yuce Qin

College of Pharmacy, Guilin Medical University

Email: info@benthamscience.net

Ruimian Ma

Institute of Basic Medical Sciences, Guilin Medical University

Email: info@benthamscience.net

Huanting Yu

College of Clinical Medicine, Guilin Medical University

Email: info@benthamscience.net

Weixue Wang

Department of Traditional Chinese Medicine, Huai'an No.3 People's Hospital

Author for correspondence.
Email: info@benthamscience.net

Xiaoxi Zhang

Institute of Basic Medical Sciences, Guilin Medical University

Author for correspondence.
Email: info@benthamscience.net

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