aspirin-eugenol-ester and Atherosclerosis

Aspirin eugenol ester (AEE) is a new drug compound synthesized by combining aspirin with eugenol. It was reported to possess anti-thrombotic, anti-atherosclerotic, and anti-oxidative effects. However, its molecular mechanism against oxidative injury is unclear. This study investigated how AEE affected the oxidative injury of vascular endothelial cells in vivo and in vitro.. A hamster model of atherosclerosis induced by a high fat diet (HFD) and an in vitro model of oxidative stress, H. AEE significantly reduced the stimulatory effect of HFD on malondialdehyde, the inhibitory effect of HFD on SOD activity and GSH/GSSG ratio, and the overexpression of inducible NOS (iNOS) in the aorta. In vitro, incubation of HUVECs with H. AEE protects vascular endothelial cells from oxidative injury by regulating NOS and Nrf2 signalling pathways. This suggests that AEE is a novel potential agent for the prevention of atherosclerosis.

Topics: Animals; Aspirin; Atherosclerosis; Cells, Cultured; Cricetinae; Diet, High-Fat; Eugenol; Human Umbilical Vein Endothelial Cells; Humans; NF-E2-Related Factor 2; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress

Based on the pro-drug principle, aspirin and eugenol were used to synthesize aspirin eugenol ester (AEE) by esterification reaction. In present study, the anti-atherosclerosis effects of AEE were investigated in hamsters with the utilization of metabonomic approach based on UPLC-Q-TOF/MS. Biochemical parameters and histopathological injures in stomach, liver and aorta were evaluated. In atherosclerotic hamster, oral administration of AEE normalized biochemical profile such as reducing TG, TCH and LDL, and significantly reduced body weight gain, alleviated hepatic steatosis and improved pathological lesions in aorta. Slight damages in stomach mucous were found in AEE group. Plasma and urine samples in control, model and AEE groups were scattered in the partial least squares-discriminate analysis (PLS-DA) score plots. Thirteen endogenous metabolites in plasma such as lysophosphatidylcholine (LysoPC), leucine and valine, and seventeen endogenous metabolites in urine such as citric acid, phenol sulphate and phenylacetylglycine were selected as potential biomarkers associated with atherosclerosis. They were considered to be in response to anti-atherosclerosis effects of AEE, mainly involved in glycerophospholipid metabolism, amino acid metabolism and energy metabolism. This study extended the understanding of endogenous alterations of atherosclerosis and offered insights into the pharmacodynamic activity of AEE.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Atherosclerosis; Biomarkers; Citric Acid; Cricetinae; Eugenol; Glycine; Leucine; Lysophosphatidylcholines; Male; Mesocricetus; Metabolome; Phenols; Valine