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Protective effects of oxymatrine on homocysteine-induced endothelial injury: Involvement of mitochondria-dependent apoptosis and Akt-eNOS-NO signaling pathways

Protective effects of oxymatrine on homocysteine-induced endothelial injury: Involvement of mitochondria-dependent apoptosis and Akt-eNOS-NO signaling pathways

Authors :
Yuan Yuan Zhu
Song Nan Jin
Guang Hai Zhou
Tian Hua Wu
Bo Wu
Kyung Woo Cho
Jin Fu Wen
Hua Yue
Source :
European Journal of Pharmacology. 864:172717
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

Homocysteine (Hcy) is an independent risk factor in the development of cardiovascular diseases (CVD). Hyperhomocysteinemia (HHcy), induces the injury of vascular endothelial cells via oxidative stress. Oxymatrine (OMT), one of the main components of Sophora flavescens, has displayed anti-inflammatory, anti-oxidant and anti-apoptotic activity. However, the effect of OMT on the Hcy-induced endothelial injury is not clearly defined yet. The aim of this study was to determine the protective effect of OMT on the Hcy-induced endothelial injury and its mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro. Methyl thiazolyl tetrazolium assay (MTT), fluorescence staining, flow cytometry and western blotting were used in this study. OMT prevented the Hcy-induced toxicity and apoptosis in HUVECs. Moreover, OMT suppressed Hcy-induced increases in reactive oxygen species, lactate dehydrogenase, malondialdehyde levels and increased superoxide dismutase levels. OMT reversed the Hcy-induced decrease in the protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2). In addition, OMT reversed the Hcy-induced apoptosis related biochemical changes such as decreased mitochondrial membrane potential and Bcl-2/Bax protein ratio, and increased protein expression of caspase-9 and caspase-3. Furthermore, OMT elevated the phosphorylation levels of Akt and eNOS, and the formation of nitric oxide (NO) in injured cells. These results suggest that OMT prevents Hcy-induced endothelial injury by regulating mitochondrial-dependent apoptosis and Akt-eNOS-NO signaling pathways concomitantly with accentuation of Nrf2 expression.

Details

ISSN :
00142999
Volume :
864
Database :
OpenAIRE
Journal :
European Journal of Pharmacology
Accession number :
edsair.doi.dedup.....be54040fe2f90cdf0ae390cc2d114824
Full Text :
https://doi.org/10.1016/j.ejphar.2019.172717