A supposed mechanism of synergistic action of catechol-containing natural polyphenols
Keywords:
catecholic phytochemicals, catechol-O-methyltransferase, chemoprevention, cytotoxicity, flavonoids, synergistic bioactivitiesAbstract
Over the past decades, accumulated evidences have been published about different synergistic biological activities between natural dietary polyphenols. Although these effects could be physiologically important in chemoprevention, cardioprotection and neuroprotection, but probably also in treatment of serious chronic diseases, such as cancer, the exact mechanisms behind this potentiation have still remained largely unknown. In this article, supposition about the involvement of phase II metabolic enzyme, catechol-O-methyltransferase (COMT), in the synergistic action of catechol-containing polyphenols is proposed. Serving as substrates, these compounds can also behave as COMT inhibitors suppressing the O-methylation of the other catechol-containing component in the combined mixture. At that, negative feedback by the increased amount of S-adenosyl-L-homocysteine generated from the methyl-group donor S-adenosyl-L-methionine during the enzymatic conversion can play an important role. Presuming that O-methylated conjugates are in general biologically less active than their unmetabolised counterparts, cotreatment of cells with combination of two catecholic natural agents can lead to a superior effect as compared to the administration of either compound alone. This mechanism can provide an explanation to the beneficial synergistic effects described for green tea extracts in chemoprevention or red wine consumption in protection of cardiovascular system in comparison with their single components tested separately. However, as currently only little is known about the possible biological activities of O-methylated conjugates of dietary polyphenolic phytochemicals, their nature and effects definitely need to be further studied. These results could prove (or disprove) the hypothesis raised in this article but also contribute to the development of physiologically or even clinically useful mixtures of polyphenols with catechol structure in the future.
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