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

Biofactors. 2007;31(2):107-16. doi: 10.1002/biof.5520310201.


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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD36 Antigens / biosynthesis
  • Cell Line
  • Down-Regulation
  • Flavones / metabolism*
  • Flavones / pharmacology*
  • Gene Expression / drug effects
  • Humans
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Scavenger / biosynthesis*
  • Receptors, Scavenger / genetics
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / metabolism


  • 3'-demethylnobiletin
  • 4'-demethylnobiletin
  • CD36 Antigens
  • Flavones
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Scavenger
  • Transcription Factor AP-1
  • nobiletin
  • tangeretin
  • Tetradecanoylphorbol Acetate