Hormesis-Mediated Mechanisms Underlying Bioactivities of Phytochemicals
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FOOD FACTORS: MOLECULAR TARGETS, MECHANISMS, PHARMACOLOGY AND IN VIVO EFFICACY (D-X HOU, SECTION EDITOR)
Hormesis-Mediated Mechanisms Underlying Bioactivities of Phytochemicals Akira Murakami 1
# Springer Nature Switzerland AG 2020
Abstract Purpose of Review 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. Recent Findings 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 nonspecific 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. Summary 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. Keywords Phytochemical . Hormesis . Adaptation . Stress . Xenobiotic
Introduction The concept of hormesis can be briefly described: “Mild stress can potentiate defensive capacity” (Fig. 1). In 1854, Rud Virchow observed an increase in the beating activity of tracheal epithelia ciliae in postmortem mucosa by introducing sodium and potassium hydroxide at low concentrations, with a concentration-dependent decrease to arrest observed at higher concentrations [1]. Similarly, in 1888, Hugo Schulz This article is part of the Topical Collection on Food Factors: Molecular targets, mechanisms, pharmacology and in vivo efficacy * Akira Murakami [email protected] 1
Department of Food Science and Nutrition School of Human Science and Environment, University of Hyogo, Himeji, Hyogo, Japan
accidentally introduced a low dose of poison to a yeast culture, which unexpectedly promoted growth. Thereafter, the term “hormesis” was coined by Chester Southam and John Ehrlich for this unique
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