Bee Bread Ameliorates Vascular Inflammation and Impaired Vasorelaxation in Obesity-Induced Vascular Damage Rat Model: The Role of eNOS/NO/cGMP-Signaling Pathway.

Zaidatul Akmal Othman,Mahaneem Mohamed,Aminah Che Romli,Joseph Bagi Suleiman,Victor Udo Nna,Zaida Zakaria,Wan Syaheedah Wan Ghazali

doi:10.3390/ijms22084225

Abstract

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role.

Highlights

Obesity has contributed to a major burden of disease in developing countries worldwide [1]
Treatment with bee bread significantly reduced these levels, which was comparable to the orlistat group, except for Highdensity lipoprotein (HDL) level, which was found to be significantly increased in OB/OR group in respect to the OB group
Our study demonstrated that bee bread treatment at 0.5 g/kg/day for 6 weeks exerted a therapeutic effect on obesity-induced impairment in ACh-mediated vasorelaxation response, in addition to ameliorating aortic inflammation and structural changes, obesity index, hyperlipidemia and atherogenic ratios

Summary

Introduction

Obesity has contributed to a major burden of disease in developing countries worldwide [1]. In the presence of high circulatory lipids, tumor necrosis factor (TNF)-α can activate nuclear factor (NF)-κβ. The acute increase in the level of NF-κβ, increases the expression of NF-κβ-derived proinflammatory markers. These include adhesion molecules and chemokine inflammatory mediators that are capable of triggering monocyte binding and infiltration into the sub-endothelial region, as well as inducing smooth muscle migration and proliferation, accelerating developing atherosclerosis by causing vascular structural and functional damages [6]. The increase in TNF-α/NF-κβ activation was seen in the aorta of rats fed with a high-fat diet (HFD) and 10% fructose-induced dyslipidemia for 12 weeks [7]

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