ReferenceID 6001

Pinocembrin mediates antiarrhythmic eﬀects in rats with isoproterenol-induced cardiac remodeling

Eur J Pharmacol

Background: High levels of circulating catecholamines are related to raise risk of cardiac arrhythmias. In addition, our recent studies have suggested that pinocembrin could decrease the susceptibility to arrhythmias in

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Reference Id: 6001
Evidence Id: 22591
Core Evidence Id: 22591
Source Reference Id: 5265
Herb2 Reference Id: HBREF006062
Subject Paper Key: HBIN039998_35183531
Pubmed Id: 35183531
Doi: 10.1016/j.ejphar.2022.174799
Paper Title: Pinocembrin mediates antiarrhythmic eﬀects in rats with isoproterenol-induced cardiac remodeling
Paper Abstract: Background: High levels of circulating catecholamines are related to raise risk of cardiac arrhythmias. In addition, our recent studies have suggested that pinocembrin could decrease the susceptibility to arrhythmias in several rat models, including chronic ischemic heart failure, myocardial infarction and depression. In this research, the effects of pinocembrin on ventricular fibrillation (VF) susceptibility were investigated in rats treated with isoproterenol (ISO) and further explored the possible mechanism. Methods: Cardiac remodeling was induced by intraperitoneally injection ISO (5 mg/kg) 7 days. Simultaneously, Rats were received pinocembrin (5 mg/kg) or saline by tail vein injection. The effects of pinocembrin were evaluated by electrocardiogram parameters, ventricular electrophysiological parameters, echocardiographic, western blot, ventricular histology, biochemical examinations. In vitro, we cultured H9C2 cardiomyocytes to further define the mechanisms. Results: Compared with ISO group, pinocembrin remarkably decreased VF inducibility rate, attenuated the shortening of QT and corrected QT (QTc) interval, action potential duration (APD), ventricular effective refractory period (ERP), and increased the protein levels of Kv4.2 and Kv4.3 and Cav1.2 and decreased phosphorylated Ca 2+ calmodulin-dependent kinase Ⅱ (p-CaMK Ⅱ). Pinocembrin also alleviated ventricular ﬁbrosis, hypertrophy and increased expression of connexin protein 43 (Cx43). In addition, pinocembrin markedly downregulated levels of malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), oxidized glutathione (GSSG) and increased the activity of superoxide dismutase (SOD) and glutathione (GSH) levels in circulation and cardiac tissue. Pinocembrin reduced the reactive oxygen species (ROS) levels. Furthermore, after treatment of pinocembrin the content of NADPH Oxidase-4 (NOX4) and NADPH Oxidase-2 (NOX2) was significantly lower and the level of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was significantly higher. In vitro, we found that Nrf2 inhibitor remarkably reduced the antioxidant effects of pinocembrin, which further demonstrated that the effect of pinocembrin was related to activation of Nrf2. Conclusion: Our data demonstrate that pinocembrin decreases ventricular electrical remodeling, ion remodeling, ventricular fibrosis, hypertrophy and suppresses isoproterenol-induced oxidative stress. The findings shown that pinocembrin mediates antiarrhythmic eﬀects in rats with isoproterenol-induced cardiac remodeling related to Nrf2/HO-1 pathway.
Journal: Eur J Pharmacol
Publish Year: 2022
Experiment Subject: rat; h9c2 cardiomyocytes
Experiment Type: Animal Experiment
Phenotype Related: Ventricular Fibrillation; Chronic Ischemic Heart Failure; Depression; Myocardial Infarction; Ventricular Fibrosis; Hypertrophy; Cardiac Arrhythmias; Arrhythmias
Paper Title Cn
Paper Title En: Pinocembrin mediates antiarrhythmic eﬀects in rats with isoproterenol-induced cardiac remodeling
Bilingual Status: semi_complete