title: Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders.
abstract: In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.
authors.affiliation: Department of Health Sciences, University of Molise, Campobasso, Italy. gscapag@gmail.com
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scapagnini
authors.forename: Sonya
authors.initials: S
authors.lastname: Vasto
authors.forename: Vasto
authors.initials: V
authors.lastname: Sonya
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
authors.forename: Abraham G
authors.initials: AG
authors.lastname: Nader
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
authors.forename: Caruso
authors.initials: C
authors.lastname: Calogero
authors.forename: Davide
authors.initials: D
authors.lastname: Zella
authors.forename: Galvano
authors.initials: G
authors.lastname: Fabio
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000178:diet therapy* / Q000503:physiopathology; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004032:Diet; D005502:Food; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000178:diet therapy* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D020218:Response Elements
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D059808:Polyphenols; D002392:Catechin; C045651:epigallocatechin gallate; D051547:Heme Oxygenase-1; D003474:Curcumin