Suppressive effects of demethylated metabolites of nobiletin on phorbol ester-induced expression of scavenger receptor genes in THP-1 human monocytic cells

摘要

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 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced SRs and adhesion molecules mRNA expression and blockade of Dil-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'-hydioxy-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-KB 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.