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Suppressive effects of demethylated metabolites of nobiletin on phorbol ester‐induced expression of scavenger receptor genes in THP‐1 human monocytic cells
Author(s) -
Eguchi Ai,
Murakami Akira,
Li Shiming,
Ho ChiTang,
Ohigashi Hajime
Publication year - 2007
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520310201
Subject(s) - cd36 , scavenger receptor , thp1 cell line , nobiletin , chemistry , receptor , flavones , gene expression , pharmacology , biochemistry , microbiology and biotechnology , biology , cell culture , gene , cholesterol , flavonoid , lipoprotein , antioxidant , chromatography , genetics
Unregulated uptake of oxidized low‐density lipoproteins (ox‐LDL) via macrophage scavenger receptors (SRs) is a key event in atherosclerosis. We previously reported that nobiletin (NOB), a citrus polymethoxylated flavone, markedly reduced 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced SRs and adhesion molecules mRNA expression and blockade of DiI‐acLDL uptake in THP‐1 human monocyte‐like cells. In this study, we examined the effects of NOB metabolites, 3 hydroxy‐5,6,7,8,4′ ‐pentamethoxyflavone (3 ‐demethyl‐NOB), 4′ ‐hydroxy‐5,6,7,8,3′ ‐pentamethoxyflavone (4′ ‐demethyl‐NOB) and 3, 4′ ‐dihydroxy‐5,6,7,8,‐tetramethoxyflavone (3, 4′ ‐didemethyl‐NOB) and NOB analog, tangeretin, on SRs and adhesion molecules mRNA expression. 3′ ‐Demethyl‐NOB significantly suppressed CD36 expression, moreover, 4′ ‐demethyl‐ and 3, 4′ ‐didemethyl‐NOB significantly suppressed TPA‐induced expression of SR‐A and LOX‐1. Further, the suppressive effects of 4′ ‐demethyl‐ and 3, 4′ ‐didemethyl‐NOB on the expression of CD36 mRNA were greater extent than parent NOB. The inhibitory effects of the metabolites toward TPA‐induced SR mRNA expression are partly associated with the suppression of AP‐1 and NF‐κB transcriptional activities. Together, our results suggest that metabolites of NOB, such as 4′ ‐demethyl‐ and 3, 4′ ‐didemethyl‐NOB, have comparable or higher potentials to attenuate SR expression than NOB.