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Tangeretin mitigates L-NAME-induced ventricular dysfunction and remodeling through AT1R/pERK1/2/pJNK signaling pathway in rats

Abstract

Tangeretin is a citrus flavonoid that exerts several beneficial effects, including anti-inflammation, anti-oxidation and neuroprotection. For this study, the aim was to test the effect of tangeretin on Nω-Nitro-L-arginine methyl ester (L-NAME)-induced high blood pressure, left ventricular dysfunction and remodeling in rats. Rats were divided into five groups (n=8/each group): a control group, an L-NAME group and three L-NAME groups treated with tangeretin (15mg/kg) or tangeretin (30 mg/kg) or captopril (5 mg/kg) for the final two weeks. After five weeks of experiment, L-NAME groups had high systolic blood pressures, ventricular dysfunction and remodeling. Overexpression of angiotensin II type 1 receptor, phosphorylated-extracellular-regulated kinase 1/2 (pERK1/2), phosphorylated-c-Jun N-terminal kinases (pJNK) protein but downregulation of endothelial nitric oxide synthase (eNOS) protein expression in ventricular tissues were shown in hypertensive rats while protein expression of phosphorylated-mitogen activated protein kinase p38 did not differ among groups. Decrease in plasma NOx and increases in vascular superoxide generation, plasma malondialdehyde, angiotensin-converting enzyme activity and angiotensin II levels were found in hypertensive rats. These alterations were suppressed in hypertensive rats treated with tangeretin or captopril. In conclusion, tangeretin exhibits antihypertensive effects and alleviates ventricular dysfunction and remodeling in hypertensive rats. These effects are associated with inhibition of renin angiotensin system activation and restoration of pERK1/2, pJNK, eNOS protein expressions along with reducing oxidative stress and raising NO bioavailability

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Article information


Submitted
09 Oct 2019
Accepted
03 Jan 2020
First published
13 Jan 2020

Food Funct., 2020, Accepted Manuscript
Article type
Paper

Tangeretin mitigates L-NAME-induced ventricular dysfunction and remodeling through AT1R/pERK1/2/pJNK signaling pathway in rats

C. Wunpathe, P. Maneesai, S. Rattanakanokchai, S. Bunbupha, U. Kukongviriyapan, T. Tong-un and P. Pakdeechote, Food Funct., 2020, Accepted Manuscript , DOI: 10.1039/C9FO02365H

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