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Sesamol reduces the atherogenicity of electronegative L5 LDL in vivo and in vitro.

Abstract
Highly electronegative low-density lipoprotein (LDL) L5 induces endothelial cell (EC) apoptosis, which leads to the development of atherosclerosis. We examined the effects of sesamol (1), a natural organic component of sesame oil, on plasma L5 levels and atherosclerosis development in a rodent model and on the L5-induced apoptosis of ECs. Syrian hamsters, which have an LDL profile similar to that of humans, were fed a normal chow diet (control), a high-fat diet (HFD), or a HFD supplemented with the administration of 50 or 100 mg/kg of 1 via oral gavage (HFD+1) for 16 weeks (n = 8 per group). Hamsters in the HFD+1 groups had reduced plasma L5 levels when compared with the HFD group. Oil Red O staining showed that atherosclerotic lesion size was markedly reduced in the aortic arch of hamsters in the HFD+1 groups when compared with that in the HFD group. In human aortic ECs, 0.3-3 μM 1 blocked L5-induced apoptosis in a dose-dependent manner. Further mechanistic studies showed that 1 inhibited the L5-induced lectin-like oxidized LDL receptor-1 (LOX-1)-dependent phosphorylation of p38 MAPK and activation of caspase-3 and increased phosphorylation of eNOS and Akt. Our findings suggest that sesamol (1) protects against atherosclerosis by reducing L5-induced atherogenicity.
AuthorsWei-Yu Chen, Fang-Yu Chen, An-Sheng Lee, Kuan-Hsiang Ting, Chia-Ming Chang, Jing-Fang Hsu, Wei-Shine Lee, Joen-Rong Sheu, Chu-Huang Chen, Ming-Yi Shen
JournalJournal of natural products (J Nat Prod) Vol. 78 Issue 2 Pg. 225-33 (Feb 27 2015) ISSN: 1520-6025 [Electronic] United States
PMID25692815 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzodioxoles
  • Lipoproteins, LDL
  • OLR1 protein, human
  • Phenols
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • sesamol
  • Caspase 3
Topics
  • Animals
  • Apoptosis (drug effects)
  • Atherosclerosis (drug therapy)
  • Benzodioxoles (blood, chemistry, pharmacology)
  • Blotting, Western
  • Caspase 3
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Endothelial Cells (drug effects)
  • Humans
  • In Vitro Techniques
  • Lipoproteins, LDL (analysis, blood, drug effects)
  • Male
  • Molecular Structure
  • Phenols (blood, chemistry, pharmacology)
  • Scavenger Receptors, Class E (blood, drug effects)

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