Hesperidin Prevents Nitric Oxide Deficiency-Induced Cardiovascular Remodeling in Rats via Suppressing TGF-β1 and MMPs Protein Expression

Abstract

Hesperidin is a major flavonoid isolated from citrus fruits that exhibits several biological activities. This study aims to evaluate the effect of hesperidin on cardiovascular remodeling induced by n-nitro l-arginine methyl ester (l-NAME) in rats. Male Sprague-Dawley rats were treated with l-NAME (40 mg/kg), l-NAME plus hesperidin (15 mg/kg), hesperidin (30 mg/kg), or captopril (2.5 mg/kg) for five weeks (n = 8/group). Hesperidin or captopril significantly prevented the development of hypertension in l-NAME rats. l-NAME-induced cardiac remodeling, i.e., increases in wall thickness, cross-sectional area (CSA), and fibrosis in the left ventricular and vascular remodeling, i.e., increases in wall thickness, CSA, vascular smooth muscle cells, and collagen deposition in the aorta were attenuated by hesperidin or captopril. These were associated with reduced oxidative stress markers, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and enhancing plasma nitric oxide metabolite (NOx) in l-NAME treated groups. Furthermore, up-regulation of tumor necrosis factor receptor type 1 (TNF-R1) and TGF- β1 protein expression and the overexpression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was suppressed in l-NAME rats treated with hesperidin or captopril. These data suggested that hesperidin had cardioprotective effects in l-NAME hypertensive rats. The possible mechanism may involve antioxidant and anti-inflammatory effects.

In‐depth proteomics approach reveals novel biomarkers of cardiac remodelling after myocardial infarction: An exploratory analysis

“…uPA is a plasmin activating pro‐matrix metalloproteinases in the cardiovascular system 26 . uPA binding to its receptor (uPAR) plays a pivotal role in signalling functions which influence cell behaviours including cell adhesion, surface proteolysis, migration, proliferation, chemotaxis and cell extravasation 27 .…”

Genistein Prevents Nitric Oxide Deficiency-Induced Cardiac Dysfunction and Remodeling in Rats

“…Subsequently, the impairment of LV function has been demonstrated in rats that have received L-NAME, supported by a reduced maximum +LVdP/dt and minimum −LVdP/dt, ejection fraction (EF), stroke volume (SV), and fraction shortening (FS) [8,9]. There is substantial evidence to support the pathological process of cardiac remodeling associated with the renin-angiotensin system (RAS), oxidative stress, and inflammation [10][11][12][13]. Angiotensin II (Ang II) induces cardiomyocyte hypertrophy via binding to angiotensin II receptor type I (AT 1 R) and activating various intracellular signaling pathways.…”

Proteomic Analysis of Heart and Kidney Tissues in Healthy and Metabolic Syndrome Rats after Hesperidin Supplementation

“…Hesperidin has been assessed in studies on rats and humans and shown to have beneficial effects on several parameters related to the cardiovascular system and the improvement of CVRFs, such as decreasing blood pressure, [ 8–11 ] improving endothelium‐dependent vasodilation during hypertension, [ 12 ] decreasing total cholesterol and triglyceride levels, [ 13 ] improving glucose and insulin levels and the homeostasis model assessment index, [ 14 ] decreasing inflammatory markers, [ 9 ] decreasing kidney damage markers, [ 15 ] and decreasing oxidative stress. [ 16 ]…”