Phytochemicals are plant secondary metabolites and have been demonstrated to exhibit versatile bioactivities in many experimental models and human studies. However, it can be pointed out that action mechanisms underlying those bioactivities remain to be fully elucidated. For instance, although the anti-oxidative effects of various types of polyphenols have long received widespread attention from food scientists, their roles in and contribution to them remain controversial because of their poor bioavailability and rapid bioconversion into biologically inactive metabolites. On the other hand, one can raise another important question as to why phytochemicals have beneficial effects for animals, including humans, since they are biosynthesized by plants as compounds necessary for adaptation to environmental stress. In regard to that fundamental question, we recently uncovered unique mechanisms of action of zerumbone, a sesquiterpene with anti-inflammatory and chemopreventive properties (1). This electrophilic agent, which has a low molecular weight (MW: 218) and simple chemical structure, was found to exhibit non-specific bindings to cysteine residues of cellular proteins (2). Such extensive protein modifications by a small molecule may disrupt the stereo-structure and functions of cellular proteins. In fact, zerumbone was demonstrated to increase E3 ubiquitin-protein ligase-dependent protein ubiquitination, a hallmark of protein denaturation and formation of aggresome (3), a cytoplasmic structure containing mis-folded proteins. Interestingly, the cells in which zerumbone adducts were loaded were shown to activate protein quality control systems for homeostasis, which is comprised of molecular chaperones, proteasome, and autophagy. More strikingly, a non-specific protein binding action of zerumbone was revealed to partially contribute to its anti-inflammatory functions via activation of heat shock factor 1 (4). This presentation highlights the stress-mediated mechanisms of phytochemicals, along with the concept of hormesis.<br/><br/>

Stress-mediated mechanisms underlying bioactivities of phytochemicals

256th National Meeting (2018)

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