Inhibition of catechol-o-methyltransferase (COMT) by myricetin, dihydromyricetin, and myricitrin

Catechol O-methyltransferase (COMT) is an important enzyme involved in the metabolism of levodopa (L-dopa) which is clinically used to treat Parkinson's disease through boosting the concentration of dopamine in the brain. Development of COMT inhibitors can efficiently increase the bioavailability of L-dopa. The present study aims to evaluate the inhibition of COMT activity by three herbal components isolated from Myrica rubra Sieb. et Zucc.. The in vitro human liver cytosol-catalyzed L-dopa methylation reaction was utilized. The results showed that all these three compounds strongly inhibited COMT activity in a concentration-dependent manner. The inhibition was competitive for these three compounds, as demonstrated by Dixon and Lineweaver-Burk plots. The inhibition kinetic parameters (Ki) towards COMT activity were calculated to be 0.5, 0.2, and 0.9 M for myricitrin, myricetin, and dihydromyricetin, respectively. From the view of structures, the deglycosylation biotransformation of myricitrin into myricetin can increase the inhibitory ability towards COMT. However, further structural alteration of myricetin towards dihydromyricetin weakens the inhibitory potential towards COMT.