Inhibition of catechol-O-methyltransferase (COMT) by some plant-derived alkaloids and phenolics

In this study, as an alternative to the medicines, natural compounds extracted from plant species (Peganum harmala, Cistus parviflorus and Vitex agnus-cactus) were investigated in order to inhibit the catechol-O-metyhltranferase (COMT) activity. In fluorometric enzyme assay, S-adenosylmethionine (SAM) and aesculetin (ES) were used as methyl donor and acceptor substrates, respectively. Their Km values were determined as 3.5 ± 0.3 μM and 6.4 ± 0.4 μM in absence of inhibitor. Inhibition performances of the plant-derived polyphenolics and alkaloids were determined. Inhibitory effect of alkaloids extracted from P. harmala seeds was found the highest among the plant extracts; however, it was lower than that of 3,5-DNC. In case of inhibition mechanism, mixed type inhibition was observed for alkaloid extract whereas uncompetitive inhibition was observed for 3,5-DNC. In case of polyphenolic extracts obtained from C. parviflorus and V. agnus-cactus leaves, mechanism were also explained as mixed type inhibition and their αKi values were calculated as 1.99 ± 0.35 μg/ml and 9.48 ± 0.58 μg/ml, respectively.