Hormetic Dietary Phytochemicals

Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Neuromolecular medicine (Impact Factor: 3.68). 07/2008; 10(4):236-46. DOI: 10.1007/s12017-008-8037-y
Source: PubMed


Compelling evidence from epidemiological studies suggests beneficial roles of dietary phytochemicals in protecting against chronic disorders such as cancer, and inflammatory and cardiovascular diseases. Emerging findings suggest that several dietary phytochemicals also benefit the nervous system and, when consumed regularly, may reduce the risk of disorders such as Alzheimer's and Parkinson's diseases. The evidence supporting health benefits of vegetables and fruits provide a rationale for identification of the specific phytochemicals responsible, and for investigation of their molecular and cellular mechanisms of action. One general mechanism of action of phytochemicals that is emerging from recent studies is that they activate adaptive cellular stress response pathways. From an evolutionary perspective, the noxious properties of such phytochemicals play an important role in dissuading insects and other pests from eating the plants. However at the subtoxic doses ingested by humans that consume the plants, the phytochemicals induce mild cellular stress responses. This phenomenon has been widely observed in biology and medicine, and has been described as 'preconditioning' or 'hormesis.' Hormetic pathways activated by phytochemicals may involve kinases and transcription factors that induce the expression of genes that encode antioxidant enzymes, protein chaperones, phase-2 enzymes, neurotrophic factors, and other cytoprotective proteins. Specific examples of such pathways include the sirtuin-FOXO pathway, the NF-kappaB pathway, and the Nrf-2/ARE pathway. In this article, we describe the hormesis hypothesis of phytochemical actions with a focus on the Nrf2/ARE signaling pathway as a prototypical example of a neuroprotective mechanism of action of specific dietary phytochemicals.

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    • "The interactions between the Nrf2-dependent antioxidant systems with other cellular signaling pathways have not been well characterized yet. But earlier studies demonstrated that few Nrf2 activators may act on upstream kinases such as phosphatidylinositol-3-kinase (PI3K), p38, protein kinase C (PKC), extracellular signal-regulated protein kinase (ERK), and c-jun N-terminal kinase (JNK), favoring the release of Nrf2 from its inhibitory protein, Keap1, and subsequent transcriptional activation of cytoprotective genes [39]. "
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    • "Activation of such hormetic neuronal pathways results in production of cytoprotective proteins, including neurotrophic factors, protein chaperones, phase II enzymes, and antiapoptotic proteins (Son et al., 2008). In this context , the flavonoid resveratrol activates multiple hormetic pathways, including stress-resistance pathways involving sirtunins, protecting neurons against ischemic injury (Kaplan et al., 2005; Parker et al., 2005). "
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    • "Traditionally, the flowers and berries have been used in folk medicine for centuries (Anonymous, 2005; Grieve, 1931; Moerman, 1998). The berries contain a wide variety of anthocyanins, flavonoids and other polyphenols (Lee and Finn, 2007; Wu et al., 2004) and these bioactive compounds have the potential to interact with stress signaling pathways and/or to upregulate endogenous defense systems (Son et al., 2008). The hydrophilic antioxidant capacity for elderberry is among the highest measured in fresh fruits/berries (Wu et al., 2004). "

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