Luteolin is a rare substrate of human catechol-O-methyltransferase favoring a para-methylation.

Scope: The study aimed to investigate the regioselectivity of methylation of luteolin (3',4',5,7-tetrahydroxyflavone) in human in vitro and in vivo.

Methods And Results: Recombinant human catechol-O-methyltransferase (COMT) and human liver S9 were utilized to study the kinetics of meta (3')- and para (4')- methylation of luteolin, and urine samples from volunteers after giving a luteolin-containing formulation were collected to determine the ratio of para-/meta-production. The results showed luteolin favored a para-methylation, with a ratio of of para-/meta-production in CLint (1.