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Nobiletin, a citrus flavonoid, suppresses phorbol ester‐induced expression of multiple scavenger receptor genes in THP‐1 human monocytic cells
Author(s) -
Eguchi Ai,
Murakami Akira,
Ohigashi Hajime
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.04.077
Subject(s) - nobiletin , thp1 cell line , flavonoid , scavenger receptor , chemistry , scavenger , receptor , phorbol , biochemistry , microbiology and biotechnology , pharmacology , signal transduction , cell culture , biology , protein kinase c , antioxidant , genetics , lipoprotein , cholesterol
Unregulated uptake of oxidized low‐density lipoproteins (ox‐LDL) via macrophage scavenger receptors (SRs) such as lectin‐like ox‐LDL receptor‐1 (LOX‐1) is a key event in atherosclerosis. In this study, we examined the effects of five selected food phytochemicals on 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced LOX‐1 mRNA expression in THP‐1 human monocyte‐like cells. Nobiletin, a citrus polymethoxylated flavone, markedly reduced it in dose‐ and time‐dependent manners. It also suppressed the phosphorylation of extracellular signal‐regulated protein kinase (ERK) 1/2, c‐Jun NH 2 ‐terminal kinase (JNK) 1/2, and c‐Jun (Ser‐63), thereby inhibiting the transcriptional activity of activator protein‐1. Further nobiletin attenuated expression of SR‐A, SR‐PSOX, CD36, and CD68, but not CLA‐1, mRNA, leading to the blockade of DiI‐acLDL uptake. Together, our results suggest that nobiletin is a promising phytochemical for regulating atherosclerosis with reasonable action mechanisms.