Diosmetin Ameliorates Vascular Dysfunction and Remodeling by Modulation of Nrf2/HO-1 and p-JNK/p-NF-κB Expression in Hypertensive Rats.

Sariya Meephat,Poungrat Pakdeechote,Putcharawipa Maneesai,Patoomporn Prasatthong,Prapassorn Potue,Sarawoot Bunbupha

doi:10.3390/antiox10091487

Sariya Meephat, Poungrat Pakdeechote + Show 4 more

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https://doi.org/10.3390/antiox10091487

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Journal: Antioxidants	Publication Date: Sep 17, 2021
Citations: 23	License type: CC BY 4.0

Affiliation: Khon Kaen University, Mahasarakham University

Abstract

Diosmetin is a citrus flavonoid that has antioxidant and anti-inflammatory effects. This study examined the effect of diosmetin on blood pressure and vascular alterations and its underlying mechanisms in experimentally hypertensive rats. Male Sprague rats were administered Nω-nitro-l-arginine methyl ester L-NAME for five weeks and were given diosmetin at doses of 20 or 40 mg/kg or captopril (5 mg/kg) for two weeks. Diosmetin alleviated hypertension, improved endothelial dysfunction, and suppressed the overactivity of sympathetic nerve-mediated vasoconstriction in aorta and mesentery hypertensive rats (p < 0.05). Increases in plasma and aortic tissue malondialdehyde (MDA) and carotid superoxide generations and reductions of plasma superoxide dismutase, catalase, and nitric oxide in hypertensive rats were ameliorated by diosmetin (p < 0.05). Diosmetin increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in hypertensive rats. Furthermore, diosmetin mitigated hypertrophy and collagen accumulation of the aortic wall in L-NAME rats. It exhibited an anti-inflammatory effect by reducing interleukin-6 (IL-6) accumulation and by overexpressing the phospho-c-Jun N-terminal kinases (p-JNK) and the phospho-nuclear factor-kappaB (p-NF-κB) proteins in the aorta (p < 0.05). Captopril was a positive control substance and had similar effects to diosmetin. In summary, diosmetin reduced blood pressure and alleviated vascular abnormalities in L-NAME-treated rats. These effects might be related to antioxidant and anti-inflammatory effects as well as to the modulation of the expression of the Nrf2/HO1 and p-JNK/NF-κB proteins.

Highlights

Introduction published maps and institutional affilHigh blood pressure is a chronic disease and a main cause of cardiovascular disease as well as vital organ damage
Sympathetic nerve-mediated contractile responses are enhanced in the vasculature isolated from nitric oxide synthase (NOS) inhibitor-treated rats, which is relevant to a high level of plasma norepinephrine and a low level of plasma Nitric oxide (NO) in these animal models [8,9,10]
This study primarily used mouse antibodies to nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), IL-6 (Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA), and phospho-c-Jun N-terminal kinases (p-JNK) and the rabbit primary antibody to p-NF-κB

Summary

Introduction

Introduction published maps and institutional affilHigh blood pressure is a chronic disease and a main cause of cardiovascular disease as well as vital organ damage. An imbalance of the vasoactive agents derived from the vascular endothelium and the overactivity of sympathetic nerve-innervated vasculature are well documented in the development and maintenance of hypertension [1]. Depletion of NO by Nω-nitro-L-arginine methyl ester (L-NAME), a non-specific nitric oxide synthase (NOS) inhibitor, has been established as a treatment to induce [3]. L-NAME causes sustained hypertension, cardiovascular dysfunction, and remodeling in animals [4,5,6,7]. Sympathetic nerve-mediated contractile responses are enhanced in the vasculature isolated from NOS inhibitor-treated rats, which is relevant to a high level of plasma norepinephrine and a low level of plasma NO in these animal models [8,9,10]

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