Authors: Eguchi, Ai | Murakami, Akira | Li, Shiming | Ho, Chi-Tang | Ohigashi, Hajime
Article Type:
Research Article
Abstract:
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.
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Keywords: Oxidized LDL, scavenger receptors, nobiletin, metabolites, demethylnobiletin
Citation: BioFactors,
vol. 31, no. 2, pp. 107-116, 2007
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