Hormetics: Dietary Triggers of an Adaptive Stress Response

Abstract

A series of dietary ingredients and metabolites are able to induce an adaptive stress response either by generation of reactive oxygen species (ROS) and/or via activation of the Nrf2/Keap1 stress response network. Most of the molecules belong to activated Michael acceptors, electrophiles capable to S-alkylate redox sensitive cysteine thiols. This review summarizes recent advances in the (re)search of these compounds and classifies them into distinct groups. More than 60 molecules are described that induce the Nrf2 network, most of them found in our daily diet. Although known as typical antioxidants, a closer look reveals that these molecules induce an initial mitochondrial or cytosolic ROS formation and thereby trigger an adaptive stress response and hormesis, respectively. This, however, leads to higher levels of intracellular glutathione and increased expression levels of antioxidant enzymes such as glutathione peroxidase, thioredoxin reductase, and superoxide dismutase. According to this principle, the author suggests the term hormetics to describe these indirect antioxidants.

Up-Regulation of Human Prostaglandin Reductase 1 Improves the Efficacy of Hydroxymethylacylfulvene, an Antitumor Chemotherapeutic Agent

“…1), a polyphenol in the spice turmeric, and resveratrol (Fig. 1), a stilbenoid in grape skins, in activating cytoprotective enzymes (Birringer, 2011). Such bioactive food components may be convenient, accessible, and efficient options for modulating desired enzymatic activities.…”

Effects of caloric restriction on oxidative stress parameters

“…The precise mechanism of anti-aging effect of caloric restriction (CR) is still unknown. Possible explanations are alteration of the insulin-like growth factor 1 (IGF-1) signaling (Bluher et al 2003;Ristow and Schmeisser 2011), sirtuin 1 (SIRT1) and mammalian target of rapamycin (mTOR) (Colman et al 2009), activation of the NF-E2-related factor 2/Kelchlike ECH-associated protein 1 (Nrf2/Keap1) (Birringer 2011), or inhibition of stress-induced apoptotic cell death (Cohen et al 2004). The effect of CR on oxidative stress (OS) parameters in organism and hormesis might have a role in anti-aging mechanism of CR (Hunt et al 2011).…”

“…Considering CR as a hormetic stressor, it is supposed that CR increases mitochondrial activity and ROS formation, and subsequent induction of ROS defense mechanisms (Birringer 2011;Ristow and Schmeisser 2011).…”

Protection or cytotoxicity mediated by a novel quinonoid-polyphenol compound?

“…These involve electron-deficient moiety favoring electron transfer from the electron-rich biomolecules, such as protein cysteine residues or low-molecular weight thiols (Bergman et al 1959). Depending on the redox properties and the applied dose range of a substance, this might result either in oxidative stress causing cell damage (a generally desired effect in case of treatment of malignancies or bacterial infection) or upregulation of the defense system, a phenomenon accompanying hormesis (Calabrese and Baldwin 1997).…”