Urolithin A shows anti-atherosclerotic activity via activation of class B scavenger receptor and activation of Nef2 signaling pathway

Background: This study investigates the therapeutic potential of urothelin A in attenuating atherosclerotic lesion in wistar rat models and explore the role of Scavenger receptor-class B type I (SR-BI) and activation of Nrf-2 singling pathway. Methods: Wistar rats (n = 48) were feed with high cholesterol diet supplemented with Vitamin D3 and subjected to balloon injury of the aorta. Three days prior to the aortal injury, rats (n = 16) were administered urothelin A (3 mg/kg/d; po). Positive control were rats receiving high cholesterol diet and balloon injury of the aorta (n = 16). The sham group (n = 16) consisted of rats fed on basal diet. After twelve weeks blood was collected from all animals for estimation of lipid and angiotensin II (Ang II) levels along, subsequently all animals were sacrificed and morphologic analysis of the aorta was performed. Expression of SR-BI and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) protein were evaluated by Western blot. Results: After twelve weeks of treatment with urolithin A, there was a significant decrease in the plasma lipid and Ang II levels and improvement of aortic lesion compared with the sham group. There was an increased expression of SR-BI and inhibition of p-ERK1/2 (p < 0.05). The expression of SR-BI was inversely correlated with levels of Ang II. Conclusion: From the results it can be safely concluded that administration of urolithin A attenuates atherosclerosis via upregulation of SR-BI expression and inhibition of p-ERK1/2 levels. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.