Jae-Hoon Choi, T. Jeong, D. Kim
Aug 1, 2003
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Influential Citations
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Journal
Journal of Cardiovascular Pharmacology
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-&kgr;B-DNA binding activity in peritoneal macrophages from Ldlr−/− mice and the activation of NF-&kgr;B in RAW264.7 macrophages. This compound suppressed plasma nitrite/nitrate levels in Ldlr−/− mice and NO production and iNOS expression in LPS+IFN&ggr;-stimulated peritoneal macrophages. Hematein treatment also suppressed the activity of iNOS promoters in RAW264.7 macrophages, and reduced the plasma levels of TNF-&agr; and IL-1&bgr; and the production of these cytokines in LPS+IFN&ggr;-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-&kgr;B activation.