Aspirin eugenol ester attenuates oxidative injury of vascular endothelial cells by regulating NOS and Nrf2 signalling pathways

Article date: April 2019

By: Mei‐Zhou Huang, Ya‐Jun Yang, Xi‐Wang Liu, Zhe Qin, Jian‐Yong Li in Volume 176, Issue 7, pages 906-918

Background and Purpose

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.

Experimental Approach

A hamster model of atherosclerosis induced by a high fat diet (HFD) and an in vitro model of oxidative stress, H2O2‐induced apoptosis of HUVECs, were used to investigate the anti‐oxidative effects of AEE.

Key Results

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 H2O2 led their apoptosis, dysfunctions of the NO systems (including increased iNOS activity, decreased endothelial NOS activity, and increased production of NO), an imbalance in calcium homeostasis and energy metabolism with an increase in intracellular free calcium and decrease in ATP, and a down‐regulation of Nrf2. In contrast, in the HUVECs pretreated with 1 μM AEE for 24 hr, the above adverse effects induced by H2O2 were significantly ameliorated. Moreover, the decrease in NO production and activity of iNOS induced by AEE was significantly attenuated in Nrf2‐inhibited HUVECs.

Conclusion and Implication

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.

DOI: 10.1111/bph.14592

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