Hormesis-Mediated Mechanisms Underlying Bioactivities of Phytochemicals

Abstract

The purpose of this review article is to highlight the importance of the concept of hormesis for more essential assimilation of mechanisms underlying the versatile bioactivities of phytochemicals. Some phytochemicals have been reported to exhibit bioactivities through activation of two key transcription factors related to hormesis, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock factor 1 (HSF1). Several reports have shown that those phytochemicals, including quercetin, resveratrol, and curcumin, up-regulated those transcription factors in a variety of animal cells. In addition, we have demonstrated that zerumbone up-regulates NRF2 for inducing antioxidative and xenobiotic-metabolizing enzymes. This agent was shown to activate HSF1 for promoting protein quality control systems via non-specific binding with cellular proteins to induce stress (proteo-stress). It is also important to note that proteo-stress induced by zerumbone contributes, at least in part, to its anti-inflammatory functions. It is intriguing that some environmental toxins have been found to possess beneficial effects when given at appropriate doses, whereas overdosed phytochemicals, including green tea catechins, have been reported to exhibit adverse effects in vivo. Mechanisms underlying the bioactivities of phytochemicals seem to be associated in part with their chemical natures as xenobiotics, while their remarkable potential to exhibit hormetic responses has been demonstrated. In other words, they can be described as a “double-edged sword,” because overdoses of phytochemicals have been shown to cause adverse effects. Therefore, it should be noted that dosage and ingestion frequencies and periods are key factors to establish in order to optimize efficacy and minimize side effects.