Aspirin Eugenol Ester Protects Vascular Endothelium From Oxidative Injury by the Apoptosis Signal Regulating Kinase-1 Pathway

Abstract

Aspirin eugenol ester (AEE) is a new potential pharmaceutical compound possessing anti-inflammatory, anti-cardiovascular disease, and antioxidative stress activity. The pharmacological activities of AEE are partly dependent on its regulation of cell apoptosis. However, it is still unclear how AEE inhibits cell apoptosis on the basis of its antioxidative stress effect. This study aimed to reveal the vascular antioxidative mechanism of AEE in response to H2O2-induced oxidative stress in HUVECs and paraquat-induced oxidative stress in rats. In the different intervention groups of HUVECs and rats, the expression of ASK1, ERK1/2, SAPK/JNK, and p38 and the phosphorylation levels of ERK1/2, SAPK/JNK, and p38 were measured. The effects of ASK1 and ERK1/2 on the anti-apoptotic activity of AEE in the oxidative stress model were probed using the corresponding inhibitors ASK1 and ERK1/2. The results showed that in the HUVECs, 200 μM H2O2 treatment significantly increased the phosphorylation of SAPK/JNK and the level of ASK1 but decreased the phosphorylation of ERK1/2, while in the HUVECs pretreated with AEE, the H2O2-induced changes were significantly ameliorated. The findings were observed in vitro and in vivo. Moreover, inhibition of ASK1 and ERK1/2 showed that ASK1 plays a vital role in the protective effect of AEE on H2O2-induced apoptosis. All findings suggested that AEE protects the vascular endothelium from oxidative injury by mediating the ASK1 pathway.

Eugenol Inhibits Ox-LDL-Induced Proliferation and Migration of Human Vascular Smooth Muscle Cells by Inhibiting the Ang II/MFG-E8/MCP-1 Signaling Cascade

“…Eugenol is a phenolic compound, which exist in various plants such as cinnamon and cloves, with extensive pharmacological activities and multiple protective effects on the cardiovascular system. [20][21][22][23][24][25][26] Eugenol can improve blood lipid metabolism, reduce oxidative stress, thereby enhancing vascular elasticity, stabilize vascular inflammation, and reduce the risk of cardiovascular disease. 16,27 Our investigation revealed that eugenol effectively suppressed the proliferation and migratory responses of HVSMCs induced by ox-LDL, thereby substantiating the anti-atherosclerotic potential of eugenol.…”

Aspirin eugenol ester affects ileal barrier function, inflammatory response and microbiota in broilers under lipopolysaccharide-induced immune stress conditions

“…Compared with the precursor drugs, AEE not only has low toxicity ( 15 ), long action time ( 16 ), and wide safety range ( 17 ), but also reduces the irritation of aspirin on the gastrointestinal tract ( 18 ) and enhances the stability of eugenol ( 19 ). Studies have shown that AEE has anti-inflammatory ( 20 ) and antioxidant ( 17 , 21 , 22 ) effects that are better than either aspirin or eugenol alone ( 23 ). In view of the fact that drugs entering the intestine always affect the intestinal microbiota ( 24 ), some researchers have conducted experiments with AEE and found that it can indeed alter the composition of the gut microbiota in mice and rats ( 25 , 26 ) and regulate the metabolomics of cecal contents and feces in rats ( 27 ).…”

Protective Effect and Mechanism of Aspirin Eugenol Ester on Lipopolysaccharide-Induced Intestinal Barrier Injury

“…For example, AEE reduced Paraquat-induced hepatotoxicity by inhibiting oxidative stress and maintaining mitochondrial function [15]. AEE protected ASK1 (apoptosis signal-regulating kinase 1) pathways by mediating vascular endothelial cells (VECs) from oxidative damage [16]. AEE pretreatment could significantly enhance the cellular superoxide dismutase and glutathione peroxidase activities in VECs [17].…”