Novel mechanisms underlying bioactivities of polyphenols via hormesis

Abstract

Polyphenols have been found in both rodent and human studies to exhibit diverse bioactivities though the mechanisms of action underlying those beneficial functions remain to be fully elucidated. Polyphenols in animals are widely recognized as xenobiotics and known to induce adaptive responses. Essential related mechanisms include expressions of antioxidative and xenobiotic-metabolizing enzymes, and heat shock proteins. Additionally, hormesis has been recognized to be an adaptive mechanism by which mild stressors can potentiate the protective capacity of the host, while those at excessive levels are harmful or lethal. Interestingly, the hormesis-related early events in lipolysis induced by polyphenols have recently been identified. For example, both curcumin and (−)-epigallocatechin-3-gallate were found to markedly decrease the amount of triglycerides in differentiated Huh7 mouse hepatoma cells. Interestingly, oxidative and protein stresses induced by those polyphenols were also demonstrated to significantly contribute to their lipolysis effects. Moreover, the key response to lipolysis was identified as a marked decrease in intracellular ATP levels. Taken together, phytochemicals may partially exhibit their bioactivities through hormesis-related mechanisms, and this hypothesis may be supported by the fact that they often show side-effects when given at high doses.