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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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Rosmarinic acid protects neurons from oxidative stress. Representative images of CGNs incubated for 24 hrs with the Bcl-2 inhibitor HA14-1 (15 M), HA14-1 + rosmarinic acid (Ros Acid; 50 M), or no treatment (Control). Immunocytochemistry was performed for β-tubulin (green) and active caspase-3 (red). Nuclei are stained with DAPI, blue. Scale bar; 10 microns.
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Figure 3: Rosmarinic acid protects neurons from oxidative stress. Representative images of CGNs incubated for 24 hrs with the Bcl-2 inhibitor HA14-1 (15 M), HA14-1 + rosmarinic acid (Ros Acid; 50 M), or no treatment (Control). Immunocytochemistry was performed for β-tubulin (green) and active caspase-3 (red). Nuclei are stained with DAPI, blue. Scale bar; 10 microns.

Mentions: Phenolic acids and diterpenes constitute another family of nutraceutical antioxidants (Figure 1C). Several of these compounds are found in rosemary, with rosmarinic acid and carnosic acid being two of the most prominent antioxidants concentrated in this herb. Rosmarinic acid has been shown to scavenge the reactive nitrogen species, peroxynitrite, and various ROS [74,75]. As a free radical scavenger, rosmarinic acid is effective at protecting SH-SY5Y human neuroblastoma cells from hydrogen peroxide-induced oxidative stress and cell death [76]. In a similar experiment to the one shown above for EGCG (see Figure 2), we have demonstrated that rosmarinic acid provides dramatic neuroprotection in the CGN model against oxidative stress and mitochondrial apoptosis induced by the Bcl-2 inhibitor, HA14-1 (Figure 3). In vivo studies using mouse models of AD and ALS have shown that rosmarinic acid significantly alleviates memory impairment associated with Aβ neurotoxicity and significantly delays disease onset and prolongs lifespan in the G93A mutant SOD1 mouse model, respectively [77,78].


Nutraceutical antioxidants as novel neuroprotective agents.

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

Rosmarinic acid protects neurons from oxidative stress. Representative images of CGNs incubated for 24 hrs with the Bcl-2 inhibitor HA14-1 (15 M), HA14-1 + rosmarinic acid (Ros Acid; 50 M), or no treatment (Control). Immunocytochemistry was performed for β-tubulin (green) and active caspase-3 (red). Nuclei are stained with DAPI, blue. Scale bar; 10 microns.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Rosmarinic acid protects neurons from oxidative stress. Representative images of CGNs incubated for 24 hrs with the Bcl-2 inhibitor HA14-1 (15 M), HA14-1 + rosmarinic acid (Ros Acid; 50 M), or no treatment (Control). Immunocytochemistry was performed for β-tubulin (green) and active caspase-3 (red). Nuclei are stained with DAPI, blue. Scale bar; 10 microns.
Mentions: Phenolic acids and diterpenes constitute another family of nutraceutical antioxidants (Figure 1C). Several of these compounds are found in rosemary, with rosmarinic acid and carnosic acid being two of the most prominent antioxidants concentrated in this herb. Rosmarinic acid has been shown to scavenge the reactive nitrogen species, peroxynitrite, and various ROS [74,75]. As a free radical scavenger, rosmarinic acid is effective at protecting SH-SY5Y human neuroblastoma cells from hydrogen peroxide-induced oxidative stress and cell death [76]. In a similar experiment to the one shown above for EGCG (see Figure 2), we have demonstrated that rosmarinic acid provides dramatic neuroprotection in the CGN model against oxidative stress and mitochondrial apoptosis induced by the Bcl-2 inhibitor, HA14-1 (Figure 3). In vivo studies using mouse models of AD and ALS have shown that rosmarinic acid significantly alleviates memory impairment associated with Aβ neurotoxicity and significantly delays disease onset and prolongs lifespan in the G93A mutant SOD1 mouse model, respectively [77,78].

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