engleski

Flavonoids-inhibitors of human butyrylcholinesterase

Introduction Butyrylcholinesterase (BChE ; 3.1.1.8) is a serine hydrolase. Its real physiological function is still unknown but it has been shown that BChE can serve as a co-regulator of cholinergic neurotransmission. Therefore, inhibition of BChE appears to be of an interest in treating diseases having symptoms of reduced neurotransmitter levels, such as the Alzheimer disease. We evaluated the BChE inhibition by seven selected flavonoids: galangin, kaempferol, quercetin, myricetin, fisetin, apigenin and luteolin ; belonging to a large family of biologically active polyphenolic compounds found in many plants and plant-derived products that are components of everyday human diet (fruits, vegetables, chocolates, herbs, red wine, tea, beer, etc.). Methods Inhibition potency was determined on BChE containing native human plasma samples. The enzyme activity was measured spectrophotometrically according to the Ellman procedure and kinetic parameters were calculated from experimental data obtained in at least three experiments. Results All flavonoids reversibly inhibited BChE. The determined enzyme-inhibitor dissociation constants (Ki) ranged from 10 &#956; M to 166 &#956; M. The inhibition potency increased in the following order: luteolin < fisetin &#8804; myricetin &#8804; quercetin < kaempferol &#8804; apigenin < galangin. Conclusions These changes in flavonoid inhibition potency were mostly connected with the number of OH groups on their side ring B. With the lowest observed Ki value of 10 &#956; M, galangin was pointed out as a promising lead in the search for new BChE inhibitors.

flavonoids; butyrylcholinesterase; inhibition

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