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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
- 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.
- Subjects :
- 0301 basic medicine
Nitric Oxide Synthase Type III
Apoptosis
Pharmacology
Nitric Oxide
medicine.disease_cause
Nitric oxide
Superoxide dismutase
03 medical and health sciences
chemistry.chemical_compound
Alkaloids
0302 clinical medicine
Enos
Human Umbilical Vein Endothelial Cells
medicine
Humans
Homocysteine
Protein kinase B
chemistry.chemical_classification
Reactive oxygen species
biology
biology.organism_classification
Mitochondria
Oxidative Stress
030104 developmental biology
Oxymatrine
chemistry
Cytoprotection
biology.protein
Proto-Oncogene Proteins c-akt
Quinolizines
030217 neurology & neurosurgery
Oxidative stress
Signal Transduction
Subjects
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