Mechanisms of Quercetin against atrial fibrillation explored by network pharmacology combined with molecular docking and experimental validation.

ABSTRACT

Atrial fibrillation (AF) is a common atrial arrhythmia for which there is no specific therapeutic drug. Quercetin (Que) has been used to treat cardiovascular diseases such as arrhythmias. In this study, we explored the mechanism of action of Que in AF using network pharmacology and molecular docking. The chemical structure of Que was obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank, STITCH, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF and normal tissue by GEO database differentially expressed genes by GEO database. The top targets were IL6, VEGFA, JUN, MMP9 and EGFR, and Que for AF treatment might involve the role of AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking showed that Que binds strongly to key targets and is differentially expressed in AF. In vivo results showed that Que significantly reduced the duration of AF fibrillation and improved atrial remodeling, reduced p-MAPK protein expression, and inhibited the progression of AF. Combining network pharmacology and molecular docking approaches with in vivo studies advance our understanding of the intensive mechanisms of Quercetin, and provide the targeted basis for clinical Atrial fibrillation treatment.