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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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Pro-survival effects of SIRT1. The schematic demonstrates the downstream consequences of nutraceutical activation of SIRT1.
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Figure 6: Pro-survival effects of SIRT1. The schematic demonstrates the downstream consequences of nutraceutical activation of SIRT1.

Mentions: The sirtuin (SIRT) proteins are a part of the histone deacetylase family and they possess (NADH)-dependent deacetylase activity. SIRT1 is a homologue of the yeast gene, silent information regulator two (Sir2), which is linked to longevity. An extra copy of the Sir2 gene in yeast can mimic a calorie-restricted diet, extending lifespan [105]. In a similar manner, caloric restriction delays neurodegenerative disease onset. Qin et al. showed that caloric restriction activated SIRT1 in the brains of AD model Tg2576 mice, and reduced amyloid neuropathology [106]. Furthermore, they showed that expression of SIRT1 in either primary Tg2576 neuronal cultures or CHO cells expressing APPsw significantly attenuated Aβ peptide formation. SIRT1 has also been linked to alleviating Aβ toxicity in cortical neuron/glial co-cultures [107]. There is still much to learn about how nutraceuticals, like resveratrol, induce SIRT1. Regardless of whether the mechanism of SIRT1 activation by resveratrol is direct [108] or indirect [109,110], induction of SIRT1 appears to be a principal mechanism underlying the neuroprotective effects of this polyphenol [111–113]. The putative pro-survival effects of SIRT1 activation are multifaceted and involve the inhibition of Aβ peptide generation, suppression of Bax-dependent apoptosis, and repression of multiple pro-apoptotic transcription factors (Figure 6) [114–118].


Nutraceutical antioxidants as novel neuroprotective agents.

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

Pro-survival effects of SIRT1. The schematic demonstrates the downstream consequences of nutraceutical activation of SIRT1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Pro-survival effects of SIRT1. The schematic demonstrates the downstream consequences of nutraceutical activation of SIRT1.
Mentions: The sirtuin (SIRT) proteins are a part of the histone deacetylase family and they possess (NADH)-dependent deacetylase activity. SIRT1 is a homologue of the yeast gene, silent information regulator two (Sir2), which is linked to longevity. An extra copy of the Sir2 gene in yeast can mimic a calorie-restricted diet, extending lifespan [105]. In a similar manner, caloric restriction delays neurodegenerative disease onset. Qin et al. showed that caloric restriction activated SIRT1 in the brains of AD model Tg2576 mice, and reduced amyloid neuropathology [106]. Furthermore, they showed that expression of SIRT1 in either primary Tg2576 neuronal cultures or CHO cells expressing APPsw significantly attenuated Aβ peptide formation. SIRT1 has also been linked to alleviating Aβ toxicity in cortical neuron/glial co-cultures [107]. There is still much to learn about how nutraceuticals, like resveratrol, induce SIRT1. Regardless of whether the mechanism of SIRT1 activation by resveratrol is direct [108] or indirect [109,110], induction of SIRT1 appears to be a principal mechanism underlying the neuroprotective effects of this polyphenol [111–113]. The putative pro-survival effects of SIRT1 activation are multifaceted and involve the inhibition of Aβ peptide generation, suppression of Bax-dependent apoptosis, and repression of multiple pro-apoptotic transcription factors (Figure 6) [114–118].

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