Naringin ameliorates endothelial dysfunction in fructose-fed rats

Abstract

Abstract. High fructose consumption is associated with metabolic disorders including hyperglycemia and dyslipidemia, in addition to endothelial dysfunction. Naringin, a flavonoid present in citrus fruit, has been reported to exhibit lipid lowering, antioxidant, and cardiovascular protective properties. Therefore, the present study investigated the effect of naringin on fructose-induced endothelial dysfunction in rats and its underlying mechanisms. Male Sprague-Dawley rats were given 10% fructose in drinking water for 12 weeks, whereas control rats were fed drinking water alone. Naringin (100 mg/kg) was orally administered to fructose fed rats during the last 4 weeks of the study. Following 12 weeks, blood samples were collected for measurement of blood glucose, serum lipid profile and total nitrate/nitrite (NOx). Vascular function was assessed by isometric tension recording. Aortic expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and nitrotyrosine were evaluated by western blot analysis. Fructose feeding induced increased levels of blood glucose, total cholesterol, triglyceride, and low density lipoprotein. In rat aortae, fructose reduced acethycholine-induced vasorelaxation, without affecting sodium nitroprusside-induced vasorelaxation. Treatment of fructose-fed rats with naringin restored fructose-induced metabolic alterations and endothelial dysfunction. Fructose-fed rats also exhibited decreased serum NOx level, reduced eNOS and p-eNOS protein expression, and enhanced nitrotyrosine expression in aortae. These alterations were improved by naringin treatment. The results of the present study suggested that naringin treatment preserves endothelium-dependent relaxation in aortae from fructose fed rats. This effect is primarily mediated through an enhanced NO bioavailability via increased eNOS activity and decreased NO inactivated to peroxynitrite in aortae.

Short‐Term Isocaloric Intake of a Fructose‐ but not Glucose‐Rich Diet Affects Bacterial Endotoxin Concentrations and Markers of Metabolic Health in Normal Weight Healthy Subjects

“…Results of several animal studies further suggest that chronic elevated fructose intake may lead to the development of NAFLD and that this at least in part results from impairments of intestinal barrier function and an increased translocation of bacterial endotoxin 25a,29. Similar relations have also been reported for fructose‐induced vascular endothelial dysfunction in rodent models . In the present study, the isocaloric exchange of complex carbohydrates of the standard diet with fructose but not glucose was associated with a significant increase of plasma endotoxin concentrations; however, LBP, l ‐citrulline, and d ‐lactate levels in plasma all shown before to be indicative of an impaired intestinal barrier function were not altered under either monosaccharide intervention.…”

Naringin Reverses High-Cholesterol Diet-Induced Vascular Dysfunction and Oxidative Stress in Rats via Regulating LOX-1 and NADPH Oxidase Subunit Expression

“…Naringin (100 mg/kg) or vehicle (1% carboxymethylcellulose) was administered daily by oral gavage for the last 4 weeks of the study (from 5 th week to 8 th week of diet treatment). The dosage of naringin was used according to previous studies [26, 27], which reported that its administration restored impaired endothelial function in rats. At the end of the experiment, the rats were anaesthetized with an intraperitoneal injection of sodium pentobarbital (50 mg/kg/BW), and blood samples were collected via cardiac puncture for the analysis of lipid levels.…”

“…Several studies have shown that it reduces the levels of plasma lipids and inflammatory markers and increases antioxidant activity in animal and human models of hyperlipidaemia [23, 24]. Additionally, naringin increased NO production which improved endothelial function in hypertensive rats [25]; normalized systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high-carbohydrate, high-fat diet-fed rats [26]; and ameliorated the impairment of endothelial function induced by high-fructose feeding [27]. Therefore, naringin is a useful compound for preventing the development and progression of atherosclerosis.…”

The Effect of YiQiFuMai on Ischemic Heart Failure by Improve Myocardial Microcirculation and Increase eNOS and VEGF Expression

“…Endothelial dysfunction occurs when myocardial NO generation decreases due to eNOS uncoupling and excessive peroxide production followed by nitrogen oxide activation [14]. Recent studies suggested that eNOS is a potential target of PI3K/AKT signaling.…”