Suppressive effects of demethylated metabolites of nobiletin on
phorbol ester-induced expression of scavenger receptor genes in THP-1 human
monocytic cells
Affiliations: Division of Food Science and Biotechnology, Graduate
School of Agriculture, Kyoto University, Kyoto, Japan | Department of Food Science, Rutgers University, New
Brunswick, NJ, USA
Note: [] Address for correspondence: Akira Murakami, Division of Food
Science and Biotechnology, Graduate School of Agriculture, Kyoto University,
Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan. Tel.: +81 75 753
6282; Fax: +81 75 753 6284; E-mail: cancer@kais.kyoto-u.ac.jp
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.
