In vitro biotransformation of flavonoids by rat liver microsomes

Xenobiotica. 1998 Apr;28(4):389-401. doi: 10.1080/004982598239498.


1. Sixteen naturally occurring flavonoids were investigated as substrates for cytochrome P450 in uninduced and Aroclor 1254-induced rat liver microsomes. Naringenin, hesperetin, chrysin, apigenin, tangeretin, kaempferol, galangin and tamarixetin were all metabolized extensively by induced rat liver microsomes but only to a minor extent by uninduced microsomes. No metabolites were detected from eriodictyol, taxifolin, luteolin, quercetin, myricetin, fisetin, morin or isorhamnetin. 2. The identity of the metabolites was elucidated using lc-ms and 1H-nmr, and was consistent with a general metabolic pathway leading to the corresponding 3',4'-dihydroxylated flavonoids either by hydroxylation or demethylation. Structural requirements for microsomal hydroxylation appeared to be a single or no hydroxy group on the B-ring of the flavan nucleus. The presence of two or more hydroxy groups on the B-ring seemed to prevent further hydroxylation. The results indicate that demethylation only occurs in the B-ring when the methoxy group is positioned at C4', and not at the C3'-position. 3. The CYP1A isozymes were found to be the main enzymes involved in flavonoid hydroxylation, whereas other cytochrome P450 isozymes seem to be involved in flavonoid demethylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aroclors
  • Biotransformation
  • Chlorodiphenyl (54% Chlorine)
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Induction
  • Flavonoids / chemistry
  • Flavonoids / metabolism*
  • In Vitro Techniques
  • Male
  • Microsomes, Liver / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Aroclors
  • Flavonoids
  • Chlorodiphenyl (54% Chlorine)
  • Cytochrome P-450 Enzyme System