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Nutraceutical antioxidants as novel neuroprotective agents.

Kelsey NA, Wilkins HM, Linseman DA - Molecules (2010)

Bottom Line: These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic.All of these compounds are generally considered to be antioxidants.Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences and Eleanor Roosevelt Institute, University of Denver, Denver, Colorado 80208, USA. nkelsey@du.edu

ABSTRACT
A variety of antioxidant compounds derived from natural products (nutraceuticals) have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.

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Proposed chemical mechanism by which organosulfur compounds dissociate Keap1 from Nrf2. HS-Protein = critical Cys residues on Keap1 which are essential for its ability to suppress Nrf2 activity. Modified from Hong et al. [91] and Rabinkov et al. [92].
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Figure 5: Proposed chemical mechanism by which organosulfur compounds dissociate Keap1 from Nrf2. HS-Protein = critical Cys residues on Keap1 which are essential for its ability to suppress Nrf2 activity. Modified from Hong et al. [91] and Rabinkov et al. [92].

Mentions: The organosulfur compounds, allicin and L-sulforaphane, share the unique ability to activate Nrf2 [91–93]. This common attribute is derived from the fact that each of these compounds has an electrophilic center which can serve as an attack site for nucleophiles, such as specific protein sulfhydryl groups present on Keap1 (Figure 5). Indeed, the mechanism of Nrf2 activation by L-sulforaphane has been demonstrated to involve disruption of the Nrf2-Keap1 interaction due to modification of critical Keap1 cysteine residues [91,94,95]. The ability of these organsulfur compounds to induce Nrf2-ARE-dependent gene transcription suggests that this pathway is essential for their neuroprotective effects.


Nutraceutical antioxidants as novel neuroprotective agents.

Kelsey NA, Wilkins HM, Linseman DA - Molecules (2010)

Proposed chemical mechanism by which organosulfur compounds dissociate Keap1 from Nrf2. HS-Protein = critical Cys residues on Keap1 which are essential for its ability to suppress Nrf2 activity. Modified from Hong et al. [91] and Rabinkov et al. [92].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697862&req=5

Figure 5: Proposed chemical mechanism by which organosulfur compounds dissociate Keap1 from Nrf2. HS-Protein = critical Cys residues on Keap1 which are essential for its ability to suppress Nrf2 activity. Modified from Hong et al. [91] and Rabinkov et al. [92].
Mentions: The organosulfur compounds, allicin and L-sulforaphane, share the unique ability to activate Nrf2 [91–93]. This common attribute is derived from the fact that each of these compounds has an electrophilic center which can serve as an attack site for nucleophiles, such as specific protein sulfhydryl groups present on Keap1 (Figure 5). Indeed, the mechanism of Nrf2 activation by L-sulforaphane has been demonstrated to involve disruption of the Nrf2-Keap1 interaction due to modification of critical Keap1 cysteine residues [91,94,95]. The ability of these organsulfur compounds to induce Nrf2-ARE-dependent gene transcription suggests that this pathway is essential for their neuroprotective effects.

Bottom Line: These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic.All of these compounds are generally considered to be antioxidants.Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences and Eleanor Roosevelt Institute, University of Denver, Denver, Colorado 80208, USA. nkelsey@du.edu

ABSTRACT
A variety of antioxidant compounds derived from natural products (nutraceuticals) have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.

Show MeSH
Related in: MedlinePlus