Schisanhenol ameliorates oxLDL-caused endothelial dysfunction by inhibiting LOX-1 signaling

Environ Toxicol. 2023 Jul;38(7):1589-1596. doi: 10.1002/tox.23788. Epub 2023 Mar 31.

Abstract

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.

Keywords: HUVECs; LOX-1; Schisanhenol; anti-inflammation; oxLDL.

MeSH terms

  • Atherosclerosis* / chemically induced
  • Cells, Cultured
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL / pharmacology
  • Nitric Oxide Synthase Type III / metabolism
  • Reactive Oxygen Species / metabolism
  • Scavenger Receptors, Class E*

Substances

  • oxidized low density lipoprotein
  • schisanhenol
  • Reactive Oxygen Species
  • Scavenger Receptors, Class E
  • Lipoproteins, LDL
  • Nitric Oxide Synthase Type III

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