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.

36 Reads
  • Source
    • "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]. "
    Hepatotoxicity: Symptoms, Management and Health Implications, Edited by Senthilkumar Rajagopal, Sengottuvelan Murugan, 06/2015: chapter 14: pages 293-317; nova., ISBN: 978-1-63482-695-2
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dietary phytochemicals, in particular flavonoids, have been suggested to limit neurodegeneration in a variety of neurological diseases and ameliorate age-related cognitive impairments. Emerging evidence suggests that absorbed dietary flavonoids and their metabolites traverse across the blood–brain barrier and exert multiple neuropharmacological actions. Flavonoids are demonstrated to influence critical signaling molecules, gene expression, and protein (kinases and enzymes) function and thereby remodulate the innate architecture of the brain to influence cognitive function and exert a neuroprotective effect. The underlying mechanism is comprised of the regulation of neuronal signaling cascades and transcription factors, which are crucial in inducing synaptic plasticity, suppression of neuroinflammatory processes, promotion of cerebrovascular perfusion, and activation of adaptive cellular stress response pathways (involving the hormetic effect) that encode expression of genes to protect against oxidative stressors. This review provides insight into the potential evidence for the association between a flavonoid-rich diet and cognitive enhancement with age-related neurodegenerative diseases.
    Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and Therapy, 1st Edition edited by Ronald R. Watson and Victor R. Preedy, 01/2015: chapter Dietary Supplements as Cognitive Enhancers The Role of Flavonoid-Rich Foods and their Relevance in Age-Related Neurodegeneration: pages 281−290; Academic Press, Elsevier., ISBN: 978-0-12-411462-3
  • Source
    • "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). "
    Acta horticulturae 01/2015; DOI:10.17660/ActaHortic.2015.1061.31
Show more

Preview (2 Sources)

36 Reads
Available from