Schisanhenol ameliorates oxLDL-caused endothelial dysfunction by inhibiting LOX-1 signaling.
Tsan-Hung ChiuChang-Wen KuTsung-Jung HoKun-Ling TsaiYi-Dung YangHsiu-Chung OuHsiu-I ChenPublished in: Environmental toxicology (2023)
Atherosclerotic lesions play a critical role in leading cardiovascular diseases. Oxidized low-density lipoprotein (OxLDL) is a vital risk factor for atherosclerosis since it acts a crucial role in endothelial dysfunction and foam cell formation. Schisanhenol, a composition extracted from the fruit of Schisandra rubriflora, has been reported to have antioxidative effects on human LDL oxidation. This study investigates whether Schisanhenol protects against oxLDL-mediated endothelial damage by modulating the lectin-like oxLDL receptor-1 (LOX-1)-mediated inflammatory processes. Human umbilical vein endothelial cells (HUVECs) were pre-treated with 10 or 20 μM Schisanhenol for 2 h and then exposed to 150 μg/mL oxLDL. We revealed that Schisanhenol reduced oxLDL-enhanced LOX-1 expression. We also found that oxLDL down-regulated endothelial nitric oxide synthase (eNOS) as well as activated inducible NOS (iNOS), thereby enhancing the generation of nitric oxide (NO). Moreover, oxLDL elevated the expression levels of phosphorylated-p38MAPK, subsequently promoting NF-κB-modulated inflammatory responses. Pretreatment with Schisanhenol exerted significant cytoprotective function in all the above-mentioned detrimental events. Results from this present study reveal that Schisanhenol has a potential therapeutic effect on preventing oxLDL-induced endothelial injuries.
Keyphrases
- endothelial cells
- low density lipoprotein
- nitric oxide synthase
- nitric oxide
- high glucose
- cardiovascular disease
- poor prognosis
- signaling pathway
- single cell
- oxidative stress
- coronary artery disease
- nuclear factor
- hydrogen peroxide
- binding protein
- gene expression
- inflammatory response
- type diabetes
- dna methylation
- mouse model
- cell therapy
- vascular endothelial growth factor
- genome wide
- pi k akt
- drug induced
- newly diagnosed
- long non coding rna