β-Elemene attenuates atherosclerosis in apolipoprotein E-deficient mice via restoring NO levels and alleviating oxidative stress

Biomed Pharmacother. 2017 Nov:95:1789-1798. doi: 10.1016/j.biopha.2017.08.092. Epub 2017 Oct 6.

Abstract

β-Elemene is a major bioactive sesquiterpenoids compound isolated from the essential oils of Curcuma Wenyujin, a Chinese medicinal herb that treats tumor in clinics. However anti-atherosclerotic effects of β-elemene have not been fully investigated in vivo. The objective of this study is to further elucidate the anti-atherosclerotic activities of β-elemene in ApoE-/- mice. Staining techniques and immunohistochemistry were used to validate atherosclerosis. Serum lipids, plasma nitrite and nitrate were analyzed by colorometric methods. ROS and antioxidative enzymes were measured through kits. Proteome profiler array was performed to analyze atherosclerosis-related inflammatory Cytokine. Western blot was used for measuring various proteins expressions. These results revealed that β-elemene inhibited atherosclerotic lesion size and increased stability of plaques in ApoE-/- mice by alleviating levels of vascular oxidative stress and preventing pro-inflammatory cytokine production. In addition β-elemene maintained endothelial function by significantly improving plasma nitrite and nitrate levels and expression of phosphorylation-eNOS in vivo. β-elemene also increased the production of the nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs) and promoted phosphorylation of eNOSser1177 and Akt in vitro. In Conclusive, data revealed that β-elemene attenuated atherosclerosis and enhanced stability of plaques at least partially through its antioxidative and anti-inflammatory features and protected against endothelial dysfunction in ApoE-/- mice.

Keywords: Apolipoprotein E-deficient mice; Atherosclerosis; Endothelial function; Nitric oxide; Oxidative stress; β-Elemene.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Apolipoproteins E / genetics*
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Curcuma / chemistry
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Lipids / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitrates / blood
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Nitrites / blood
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Apolipoproteins E
  • Lipids
  • Nitrates
  • Nitrites
  • Reactive Oxygen Species
  • Sesquiterpenes
  • beta-elemene
  • Nitric Oxide
  • Nitric Oxide Synthase Type III