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Anticholinesterase activity of selected phenolic acids and flavonoids - interaction testing in model solutions.

INTRODUCTION
Alzheimer's disease is a progressively developing neurodegenerative disorder of the central nervous system. The only present treatment of this disease is the use of acetyl- and butyrylcholinesterase inhibitors. Previously, the neuroprotection of phenolic acids and flavonoids in the brain has been indicated.


MATERIALS AND METHOD
This study measured anticholinesterase activities of 9 phenolic acids and 6 flavonoids, singly or in combination. The synergy/antagonism/zero interaction between compounds was evaluated taking into consideration the statistical significance. Ellman's modified spectrophotometric method was used with the simultaneous measurement of the false-positive effect of compounds.


RESULTS
The anti-acetylcholinesterase activity of phenolic acids was as follows: homogentisic acid > 4-hydroxyphenylpyruvic acid > nordihydroguaiaretic acid > rosmarinic acid > caffeic acid > gallic acid = chlorogenic acid > homovanillic acid > sinapic acid. p-Hydroxyphenylpyruvic, caffeic, chlorogenic, gentisic, homogentisic, nordihydroguaiaretic and rosmarinic acids in pairs exhibited, in most cases, a lower inhibitory activity (at p>0.05), than the sum of the activities of single compounds. Also, phenolic acids in pairs with flavonoids (cyanidin, delphinidin, kaempferol, myricetin, phloridzin, pelargonidin or quercetin) presented, in most cases, a lower inhibitory activity than could be calculated for both compounds singly (at p>0.05). Only in the case of a few samples was the inhibitory activity of two compounds higher than the sum of inhibitions exerted by the same compounds tested singly (either at p>0.05 or p<0.05). The lack of synergy of pairs of inhibitors suggests one small binding site, making impossible to accommodate both inhibitors adjacent to one another.