Nobiletin metabolite, 3',4'-dihydroxy-5,6,7,8-tetramethoxyflavone, inhibits LDL oxidation and down-regulates scavenger receptor expression and activity in THP-1 cells.

doi:10.1016/j.bbalip.2009.10.002

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 生物科技系(所) > 期刊論文 > Item 310902800/25160

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標題:	Nobiletin metabolite, 3',4'-dihydroxy-5,6,7,8-tetramethoxyflavone, inhibits LDL oxidation and down-regulates scavenger receptor expression and activity in THP-1 cells.
作者:	Ya-Hsuan Lo Min-Hsiung Pan Shiming Li Jui-Hung Yen Mei-Chun Kou Chi-Tang Ho Ming-Jiuan Wu
貢獻者:	生物科技系
關鍵字:	Low-density lipoprotein (LDL) Atherogenesis Scavenger receptor A (SR-A) CD36
日期:	2010-02
上傳時間:	2012-03-30 15:17:50 (UTC+8)
出版者:	Elsevier
摘要:	There is accumulating evidence that LDL oxidation is essential for atherogenesis and antioxidants that prevent oxidation may either decelerate or reduce atherogenesis. Current study focused on the effect and mechanism of 3′,4′-dihydroxy-5,6,7,8-tetramethoxyflavone (DTF), a major metabolite of nobiletin (NOB, a citrus polymethoxylated flavone) on atherogenesis. We found DTF had stronger inhibitory activity than α-tocopherol on inhibiting Cu2+-mediated LDL oxidation measured by thiobarbituric acid-reactive substances assay (TBARS), conjugated diene formation and electrophoretic mobility. Monocyte-to-macrophage differentiation plays a vital role in early atherogenesis. DTF (10–20 μM) dose-dependently attenuated differentiation along with the reduced gene expression of scavenger receptors, CD36 and SR-A, in both PMA- and oxidized low-density lipoprotein (oxLDL)-stimulated THP-1 monocytes. Furthermore, DTF treatment of monocytes and macrophages led to reduction of fluorescent DiI-acLDL and DiI-oxLDL uptake. In conclusion, at least three mechanisms are at work in parallel: DTF reduces LDL oxidation, attenuates monocyte differentiation into macrophage and blunts uptake of modified LDL by macrophage. The effect is different from that of NOB, from which DTF is derived. This study thus significantly enhanced our understanding on how DTF may be beneficial against atherogenesis.
關聯:	Biochimica et Biophysica Acta 1801(2)：p.114-126
显示于类别:	[生物科技系(所)] 期刊論文

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