Abstract | BACKGROUND: 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 Ca2+ 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 (H2O2), 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:
|
Authors | Xiaoli Chen, Weiguo Wan, Qian Ran, Tianxin Ye, Yazhou Sun, Zhangchi Liu, Xin Liu, Shaobo Shi, Chuan Qu, Cui Zhang, Bo Yang |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 920
Pg. 174799
(Apr 05 2022)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 35183531
(Publication Type: Journal Article)
|
Copyright | Copyright © 2022 Elsevier B.V. All rights reserved. |
Chemical References |
- Flavanones
- NF-E2-Related Factor 2
- pinocembrin
- Hydrogen Peroxide
- Isoproterenol
|
Topics |
- Animals
- Flavanones
(pharmacology, therapeutic use)
- Hydrogen Peroxide
(pharmacology)
- Isoproterenol
(pharmacology)
- Myocytes, Cardiac
(metabolism)
- NF-E2-Related Factor 2
(metabolism)
- Oxidative Stress
- Rats
- Ventricular Remodeling
|