title: Hematein inhibits atherosclerosis by inhibition of reactive oxygen generation and NF-kappaB-dependent inflammatory mediators in hyperlipidemic mice.
abstract: Hematein, a natural compound, is a known anti-inflammatory and antiatherogenic agent in the rabbit model. The authors investigated the effects of this compound on atherogenesis and possible mechanisms of the actions in the hyperlipidemic mice. Low-density lipoprotein receptor-deficient (Ldlr-/-) mice fed a high-cholesterol diet alone for 8 weeks developed the fatty streak lesion in the aortic sinus, whereas this lesion was significantly reduced by hematein treatment without a change in plasma lipid levels compared with control mice. Hematein treatment reduced plasma levels of lipid peroxide and superoxide generation in LPS-stimulated peritoneal macrophage. Hematein treatment inhibited NF-kappaB-DNA binding activity in peritoneal macrophages from Ldlr-/- mice and the activation of NF-kappaB in RAW264.7 macrophages. This compound suppressed plasma nitrite/nitrate levels in Ldlr-/- mice and NO production and iNOS expression in LPS+IFNgamma-stimulated peritoneal macrophages. Hematein treatment also suppressed the activity of iNOS promoters in RAW264.7 macrophages, and reduced the plasma levels of TNF-alpha and IL-1beta and the production of these cytokines in LPS+IFNgamma-stimulated peritoneal macrophages. These results suggest that hematein inhibits atherosclerotic lesion formation, possibly by reducing proinflammatory mediators through a decrease in reactive oxygen species generation and NF-kappaB activation.
authors.affiliation: Department of Veterinary Pathology, College of Veterinary Medicine and Agricultural Biotechnology, Seoul National University, Suwon, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Tae-Sook
authors.initials: TS
authors.lastname: Jeong
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Na
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Nam
authors.forename: Sae-Bom
authors.initials: SB
authors.lastname: Lee
authors.forename: Hyoung-Chin
authors.initials: HC
authors.lastname: Kim
authors.forename: Sei Ryang
authors.initials: SR
authors.lastname: Oh
authors.forename: Yang-Kyu
authors.initials: YK
authors.lastname: Choi
authors.forename: Song-Hae
authors.initials: SH
authors.lastname: Bok
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D002791:Cholesterol, Dietary / Q000097:blood*; D005260:Female; D006416:Hematoxylin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000627:therapeutic use*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*
chemical_list: D002791:Cholesterol, Dietary; D018836:Inflammation Mediators; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C007915:hematein; D006416:Hematoxylin