The Interaction of Urolithins and its Metabolites with Cholinesterase and the Oxidative Stress Mechanisms

The beneficial effects of ellagitannin rich diet has been known for the treatment of Alzheimer Disease. Regarding the lack of bioavailability of ellagitannins and their in gastrointestinal tract to urolithins, these biological effects are attributed to the bioavailable urolithin derivatives. Urolithins are benzo[c]chromen-6-one derivatives, with hydroxyl substitutions. Within this study, we have synthesized the major urolithins, their methyl ether metabolites, concomitant to some synthetic analogues. The potential of compounds to inhibit cholinesterases, monoamine oxidase-B, cyclooxygenase enzymes were investigated. Besides, their antioxidant activities were also evaluated in DPPH antioxidant assay system. The results for the first time described a structure activity relationship in some of the biological activities of urolithins. Furthermore, a mechanistic approach for the action of ellagitannin rich food for the treatment and preventation from Alzheimer Disease was also provided. Keywords: alzheimer disease, urolithin, benzo[c]chromen-6-one, cholinesterases, cyclooxygenase enzymes, monoamine oxidase-B, DPPH antioxidant, urolithin.