Nobiletin, a citrus flavonoid, suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells.

Abstract

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.

• Authors: Ai Eguchi, Akira Murakami, Hajime Ohigashi
• Journal: FEBS letters (FEBS Lett) Vol. 580 Issue 13 Pg. 3321-8 (May 29 2006) ISSN: 0014-5793 [Print] England
• PMID: 16698017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbocyanines
• Cell Adhesion Molecules
• Flavones
• Flavonoids
• Hypolipidemic Agents
• Lipoproteins, LDL
• OLR1 protein, human
• Phorbol Esters
• RNA, Messenger
• Receptors, Scavenger
• Scavenger Receptors, Class E
• Transcription Factor AP-1
• 3,3'-dioctadecylindocarbocyanine
• nobiletin
• Mitogen-Activated Protein Kinases
• Tetradecanoylphorbol Acetate

Topics

• Carbocyanines (metabolism)
• Cell Adhesion Molecules (genetics, metabolism)
• Cells, Cultured
• Citrus (chemistry)
• Flavones (pharmacology)
• Flavonoids (pharmacology)
• Gene Expression (drug effects)
• Humans
• Hypolipidemic Agents (pharmacology)
• Lipoproteins, LDL (metabolism)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Monocytes (drug effects, metabolism)
• Phorbol Esters (pharmacology)
• Phosphorylation (drug effects)
• RNA, Messenger (metabolism)
• Receptors, Scavenger (antagonists & inhibitors, genetics)
• Scavenger Receptors, Class E (antagonists & inhibitors, genetics)
• Tetradecanoylphorbol Acetate (pharmacology)
• Transcription Factor AP-1 (antagonists & inhibitors)
• Transcription, Genetic