Aspirin Eugenol Ester Reduces H₂O₂-Induced Oxidative Stress of HUVECs via Mitochondria-Lysosome Axis

Abstract

The oxidative stress of vessel endothelium is a major risk factor of cardiovascular disorders. Antioxidative stress drugs are widely used in cardiovascular therapy. Aspirin eugenol ester (AEE) is a new pharmaceutical compound synthesized by esterification reaction of aspirin with eugenols and possesses antioxidative activity. The present study was designed to investigate the mechanism how AEE protects human umbilical vein endothelial cells (HUVECs) from H2O2-induced oxidative stress. H2O2 was given to the HUVECs with or without AEE pretreatment. Changes in the oxidative stress-related factors, including those related to the mitochondria-lysosome axis, were determined with Western blotting, cellular immunofluorescence, and enzyme activity test. The results showed that, in the HUVECs, 300 μM H2O2 treatment significantly increased the apoptosis rate, MDA concentration, reactive oxygen species (ROS) production, mitochondrial membrane potential, expression of Bax and mature cathepsin D (CTSD), and activity of CTSD and Caspase3 (Cas3) but decreased the expression of Bcl2 and lysosomal membrane stability, while in the HUVECs pretreated with AEE, the above changes caused by either the stimulatory or the inhibitory effect of H2O2 on the relevant factors were significantly reduced. AEE pretreatment significantly enhanced the activity of cellular superoxide dismutase and glutathione peroxidase in the HUVECs. Our findings suggest that AEE effectively reduced H2O2-induced oxidative stress in the HUVECs via mitochondria-lysosome axis.

An Advanced Mode of Antioxidants Delivery System Effective in the Treatment of ROS and Skin Permeation of The Cosmetic Formulations - The Possible Application of Clove Oil, Eugenol and New Eugenol Derivative

“…The transport of the active substance (contained in the cosmetic formulation) the skin also depends on the molecular weight of the active substance itself. Overcoming the lipophilic barrier, which is the skin, is possible for eugenol and non-polar -new ester of eugenol, which have molecular weights of <600 Da [18,45,54,58]. Besides better absorption of active substance by penetrating faster, the presented cosmetic formulations can provide endogenous action against free radicals, which is their superiority to the used in cosmetology pure acids (α-and β-hydroxy acids, TChAA), for which the skin is a barrier limiting their penetration [18,46,49,53,58].…”

“…Due to the content of phenolic compounds (eugenol) they may also show chemopreventive activity and affect the induction of cancer cell apoptosis [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57].…”

“…In addition, the presence of chlorine atoms in the structure of EDChA changes the electro-neutrality of carbon atoms. Moreover, the presence of the methoxy group (-OCH3) in the eugenol and its ester increases the antioxidant properties of these compounds [54].…”

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

“…Aspirin eugenol ester (AEE) is a newly discovered potential pharmaceutical compound possessing anti-inflammatory, anti-cardiovascular disease, and antioxidative stress pharmacological activities ( Li et al, 2011 ; Li et al, 2012b ; Ma et al, 2015 ; Ma et al, 2017 ; Huang et al, 2019a ). In the H 2 O 2 -induced oxidative stress model using human umbilical vein endothelial cells (HUVECs), the protective effect of AEE on vascular oxidative injury is synchronized with the AEE-enhanced expression of Bcl2 and Nrf2 ( Huang et al, 2019a ; 2019c ). It has been well documented that AEE can alleviate H 2 O 2 -induced dysfunction in mitochondria, the generation of ROS production and the increase in apoptosis rate by enhancing the expression of Bcl2 and Nrf2 ( Huang et al, 2019a ; 2019c ).…”

“…In the H 2 O 2 -induced oxidative stress model using human umbilical vein endothelial cells (HUVECs), the protective effect of AEE on vascular oxidative injury is synchronized with the AEE-enhanced expression of Bcl2 and Nrf2 ( Huang et al, 2019a ; 2019c ). It has been well documented that AEE can alleviate H 2 O 2 -induced dysfunction in mitochondria, the generation of ROS production and the increase in apoptosis rate by enhancing the expression of Bcl2 and Nrf2 ( Huang et al, 2019a ; 2019c ). Mitochondrial dysfunction can induce the release of cytochrome C, apoptosis-inducing factor (AIF), and other factors into the cytoplasm to mediate downstream apoptotic signals that cause cell apoptosis ( Chong et al, 2003 ; Chua et al, 2009 ; Choudhury et al, 2010 ; Cuadrado and Nebreda, 2010 ; Abate et al, 2019 ; Hasnat et al, 2019 ), and the exacerbation of reactive oxygen species (ROS) production induced by mitochondrial dysfunction is vital to cell apoptosis ( Jaeschke and Bajt, 2006 ; Kim et al, 2006 ; Lai et al, 2012 ; Meng et al, 2018 ; Moradzadeh et al, 2018 ).…”