Citrus flavonoid, 5-demethylnobiletin, suppresses scavenger receptor expression in THP-1 cells and alters lipid homeostasis in HepG2 liver cells.

doi:10.1002/mnfr.201000226

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > Periodical Articles > Item 310902800/26690

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题名:	Citrus flavonoid, 5-demethylnobiletin, suppresses scavenger receptor expression in THP-1 cells and alters lipid homeostasis in HepG2 liver cells.
作者:	Yen, Jui-Hung Weng, Ching-Yi Li, Shiming Lo, Ya-Hsuan Pan, Min-Hsiung Fu, Shih-Hang Ho, Chi-Tang Wu2, Ming-Jiuan
贡献者:	生物科技系
关键词:	Acyl CoA:diacylglycerol acyltransferase 2 Atherogenesis CD36 c-Jun NH2-terminal kinase Steroid-response element-binding protein-2
日期:	2011-05
上传时间:	2013-06-05 16:42:46 (UTC+8)
出版者:	Wiley Wiley-Blackwell
摘要:	Scope: Nobiletin, a polymethoxyflavone from the peel of citrus fruits, has been reported to inhibit modified LDL uptake in macrophages and enhance hepatic LDL receptor expression and activity. We report the anti-atherogenic effect and mechanism of 5-demethylnobiletin, an auto-hydrolysis product of nobiletin. Methods and results: 5-Demethylnobiletin significantly attenuated phorbol 12-myristate 13-acetate-induced gene expression and activity of scavenger receptors, CD36, scavenger receptor-A and lectin-like oxidized LDL receptor-1. The inhibitory effect is partly associated with the inhibition of protein-kinase C activity and c-Jun NH2-terminal kinase 1/2 phosphorylation, thereby inhibiting the activation of activator protein-1 and nuclear factor-κB. 5-Demethylnobiletin treatment also led to reduction of oxidized LDL-induced CD36 mRNA expression and blockade of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanide perchlorate-modified LDL uptake in THP-1-derived macrophages. In the human hepatoma cell line HepG2, 5-demethylnobiletin significantly induced LDL receptor activity and transcription, at least in part, through steroid-response element-binding protein-2 activation. 5-Demethylnobiletin also decreased the mRNA expression of acyl CoA:diacylglycerol acyltransferase 2, the key enzyme involved in the hepatic triacylglycerol biosyntheses. Conclusion: Current results suggest that 5-demethylnobiletin has diverse anti-atherogenic bioactivities. It is more potent in inhibiting monocyte-to-macrophage differentiation and foam cell formation than its permethoxylated counterpart, nobiletin. It exhibits similar hypolipidemic activity as nobiletin and both can enhance LDL receptor gene expression and activity and decreased acyl CoA:diacylglycerol acyltransferase 2 expression.
關聯:	Molecular Nutrition & Food Research 55(5), pp.733-748
显示于类别:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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