title: 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.
authors.affiliation: Graduate Institute of Basic Medical Science, ‡Graduate Institute of Clinical Medical Science, and ∇Department of Biological Science and Technology, College of Life Sciences, China Medical University , No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Chen
authors.forename: An-Sheng
authors.initials: AS
authors.lastname: Lee
authors.forename: Kuan-Hsiang
authors.initials: KH
authors.lastname: Ting
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Chang
authors.forename: Jing-Fang
authors.initials: JF
authors.lastname: Hsu
authors.forename: Wei-Shine
authors.initials: WS
authors.lastname: Lee
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy*; D052117:Benzodioxoles / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000032:analysis / Q000097:blood / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D010636:Phenols / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D051127:Scavenger Receptors, Class E / Q000097:blood / Q000187:drug effects
chemical_list: D052117:Benzodioxoles; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D010636:Phenols; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C025583:sesamol; D053148:Caspase 3