Nobiletin, a citrus flavonoid, suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells.
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 NH2-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.
Eguchi
Ai
A
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Murakami
Akira
A
Ohigashi
Hajime
H
D002232:Carbocyanines / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002957:Citrus / Q000737:chemistry; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors* / Q000235:genetics; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic
D002232:Carbocyanines; D015815:Cell Adhesion Molecules; D047309:Flavones; D005419:Flavonoids; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D010703:Phorbol Esters; D012333:RNA, Messenger; D051116:Receptors, Scavenger; D051127:Scavenger Receptors, Class E; D018808:Transcription Factor AP-1; C024286:3,3'-dioctadecylindocarbocyanine; C008661:nobiletin; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate