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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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Modulation of pro-survival protein kinase pathways by nutraceuticals.
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Figure 8: Modulation of pro-survival protein kinase pathways by nutraceuticals.

Mentions: There are a number of additional signaling cascades that have been shown to be modulated by nutraceutical antioxidants including the predominantly pro-survival MEK/ERK and PI3K/AKT pathways, reviewed by Spencer [125]. For instance, resveratrol protects HT22 hippocampal cells from glutamate-induced oxidative stress via a PI3K/AKT-dependent induction of SOD2 [126]. Similarly, EGCG rescues retinal ganglion cells from axotomy-induced injury through activation of both PI3K/AKT and MEK/ERK pro-survival pathways [127]. Downstream of each of these pathways lies the transcription factor, cAMP-response element binding protein (CREB), which can induce the expression of key pro-survival genes like Bcl-2 [128,129]. Consistent with a role for this pathway in the neuroprotective effects of nutraceuticals, long term administration of green tea catechins in drinking water significantly increased CREB activity and decreased Aβ oligomer production in a mouse model of early onset deficits in learning and memory [130]. The characteristic of nutraceuticals to modulate key pro-survival kinase pathways likely plays a significant role in their neuroprotective actions (Figure 8).


Nutraceutical antioxidants as novel neuroprotective agents.

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

Modulation of pro-survival protein kinase pathways by nutraceuticals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: Modulation of pro-survival protein kinase pathways by nutraceuticals.
Mentions: There are a number of additional signaling cascades that have been shown to be modulated by nutraceutical antioxidants including the predominantly pro-survival MEK/ERK and PI3K/AKT pathways, reviewed by Spencer [125]. For instance, resveratrol protects HT22 hippocampal cells from glutamate-induced oxidative stress via a PI3K/AKT-dependent induction of SOD2 [126]. Similarly, EGCG rescues retinal ganglion cells from axotomy-induced injury through activation of both PI3K/AKT and MEK/ERK pro-survival pathways [127]. Downstream of each of these pathways lies the transcription factor, cAMP-response element binding protein (CREB), which can induce the expression of key pro-survival genes like Bcl-2 [128,129]. Consistent with a role for this pathway in the neuroprotective effects of nutraceuticals, long term administration of green tea catechins in drinking water significantly increased CREB activity and decreased Aβ oligomer production in a mouse model of early onset deficits in learning and memory [130]. The characteristic of nutraceuticals to modulate key pro-survival kinase pathways likely plays a significant role in their neuroprotective actions (Figure 8).

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