Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits

Objective: Recent advances have established a fundamental role for inflammation in mediating all stages of atherosclerosis, from initiation through progression. Quercetin may be a powerful bioactive constituent of the human diet, as a free radical scavenging agent and through interactions with various endogenous proteins. The present study focused on the effect of quercetin on inflammation induced by a hypercholesterolemic diet (HCD) in rabbits. Methods: The animals were subjected to two different experiments, atherosclerotic progression and regression. In the atherosclerotic progression study, quercetin (25 mg/kg of body weight) was administered with the HCD for 90 d. In the atherosclerotic regression study, the animals were fed with the HCD for 90 d and then supplemented with quercetin (25 mg/kg of body weight) for another 90 d. The inflammatory enzyme activities were examined and a histopathologic examination of the aorta was performed. Results: In the atherosclerotic progression study, quercetin coadministered with the HCD significantly decreased the activities of inflammatory enzymes such as cyclooxygenase, lipoxygenases (LOX) such as 5-LOX and 12-LOX in monocytes, nitric oxide synthase activity in the plasma, myeloperoxidase activity in the aorta, and the level of C-reactive protein in serum. In the regression study, quercetin administration significantly decreased the increased activities of inflammatory mediators such as cyclooxygenase, 5-LOX, 12-LOX, myeloperoxidase, and nitric oxide synthase and the serum level of C-reactive protein in HCD-fed rabbits compared with regression control rabbits. This effect was confirmed by histopathologic examination of the aorta. Conclusion: This study demonstrates that quercetin modulates the deleterious inflammatory effects induced by an HCD in vivo in rabbits, suggesting its beneficial effect in decreasing inflammation in atherosclerotic progression and regression. (C) 2013 Elsevier Inc. All rights reserved.