engleski

Evaluation of flavonoids potency to inhibit human butyrylcholinesterase

Butyrylcholinesterase (BChE ; 3.1.1.8) is a serine hydrolase that belongs to the lipase/protease family with &#945; /&#946; -hydrolase fold. Opposite to the key role in cholinergic neurotransmission of its sister enzyme, acetylcholinesterase (AChE ; 3.1.1.7), the real physiological function of BChE is yet unknown. However, it has been shown that BChE can also hydrolyse the native substrate of AChE, neurotransmitter acetylcholine, and thus serve as a co-regulator of cholinergic transmission. This is why the inhibition of BChE, not only of AChE, appears to be of an interest in treating diseases having symptoms of reduced acetylcholine 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.). Inhibition potency was determined on BChE containing native human plasma samples. Results of our experiments showed that all tested flavonoids reversibly inhibited BChE and the evaluated enzyme-inhibitor dissociation constants (Ki) ranged from 10 &#956; M to 140 &#956; M. The inhibition potency increased in the following order: luteolin<fisetin<myricetin<quercetin<kaempferol<apigenin<galangin. 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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