Hematein inhibits atherosclerosis by inhibition of reactive oxygen generation and NF-kappaB-dependent inflammatory mediators in hyperlipidemic mice.
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.
Choi
Jae-Hoon
JH
Department of Veterinary Pathology, College of Veterinary Medicine and Agricultural Biotechnology, Seoul National University, Suwon, Korea.
Jeong
Tae-Sook
TS
Kim
Dae-Yong
DY
Kim
Young-Myeong
YM
Na
Hee-Jun
HJ
Nam
Ki-Hwan
KH
Lee
Sae-Bom
SB
Kim
Hyoung-Chin
HC
Oh
Sei Ryang
SR
Choi
Yang-Kyu
YK
Bok
Song-Hae
SH
Oh
Goo Taeg
GT
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*
D002791:Cholesterol, Dietary; D018836:Inflammation Mediators; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C007915:hematein; D006416:Hematoxylin