1. Protective effects of oxymatrine on homocysteine-induced endothelial injury: Involvement of mitochondria-dependent apoptosis and Akt-eNOS-NO signaling pathways.
- Author
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Wu B, Yue H, Zhou GH, Zhu YY, Wu TH, Wen JF, Cho KW, and Jin SN
- Subjects
- Cytoprotection drug effects, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells metabolism, Humans, Mitochondria drug effects, Mitochondria metabolism, Oxidative Stress drug effects, Signal Transduction drug effects, Alkaloids pharmacology, Apoptosis drug effects, Homocysteine adverse effects, Human Umbilical Vein Endothelial Cells drug effects, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Proto-Oncogene Proteins c-akt metabolism, Quinolizines pharmacology
- 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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