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Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: a comprehensive review.

Venkatesan R, Ji E, Kim SY - Biomed Res Int (2015)

Bottom Line: Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease.Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75(NTR) superfamily.We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Gachon University, No. 191, Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea.

ABSTRACT
Alzheimer's disease (AD), characterized by progressive dementia and deterioration of cognitive function, is an unsolved social and medical problem. Age, nutrition, and toxins are the most common causes of AD. However, currently no credible treatment is available for AD. Traditional herbs and phytochemicals may delay its onset and slow its progression and also allow recovery by targeting multiple pathological causes by antioxidative, anti-inflammatory, and antiamyloidogenic properties. They also regulate mitochondrial stress, apoptotic factors, free radical scavenging system, and neurotrophic factors. Neurotrophins such as BDNF, NGF, NT3, and NT4/5 play a vital role in neuronal and nonneuronal responses to AD. Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease. Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75(NTR) superfamily. We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection. Although these phytochemicals have attracted attention owing to their in vitro neurotrophin potentiating activity, their in vivo and clinical efficacy trials has yet to be established. Therefore, further research is necessary to prove the neuroprotective effects in preclinical models and in humans.

No MeSH data available.


Related in: MedlinePlus

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Mentions: Lemon balm, the common name for Melissa officinalis, has been used traditionally for its antioxidant and neuroprotective actions. For example, rosmarinic acid has been shown to scavenge free radicals and prevent apoptosis [99]. Rosmarinic acid (Figure 7) from Rosmarinus officinalis exhibits a mimetic neurotrophic effect in PC12 cells by inducing ERK1/2-mediated cell differentiation and enhancing cholinergic activity [100]. Previous studies have demonstrated that M. officinalis contains rosmarinic, ursolic, and oleanolic acids, which increases the number of cells and promotes the differentiation of neuroblasts in the dentate gyrus by modulating serum gamma-aminobutyric acid (GABA) transaminase and corticosterone levels [83]. A recent study has revealed that lemon balm oil extracts contain citronellal, geraniol, geranyl acetate, isogeranial, ε-caryophyllene, caryophyllene oxide, germacrene D, and carvacrol [101]. These compounds protect against neuronal damage from hypoxia-induced proinflammatory cytokines such as IL-1β and TNF-α and caspase 3 activity by suppressing hypoxia inducible factor-1α (HIF-1α) expression [102]. Taken together, these studies show that rosmarinic acid from M. officinalis and its derivatives play a vital role in the mechanisms that underlie memory enhancing function by improving cholinergic activity.


Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: a comprehensive review.

Venkatesan R, Ji E, Kim SY - Biomed Res Int (2015)

© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4446472&req=5

Mentions: Lemon balm, the common name for Melissa officinalis, has been used traditionally for its antioxidant and neuroprotective actions. For example, rosmarinic acid has been shown to scavenge free radicals and prevent apoptosis [99]. Rosmarinic acid (Figure 7) from Rosmarinus officinalis exhibits a mimetic neurotrophic effect in PC12 cells by inducing ERK1/2-mediated cell differentiation and enhancing cholinergic activity [100]. Previous studies have demonstrated that M. officinalis contains rosmarinic, ursolic, and oleanolic acids, which increases the number of cells and promotes the differentiation of neuroblasts in the dentate gyrus by modulating serum gamma-aminobutyric acid (GABA) transaminase and corticosterone levels [83]. A recent study has revealed that lemon balm oil extracts contain citronellal, geraniol, geranyl acetate, isogeranial, ε-caryophyllene, caryophyllene oxide, germacrene D, and carvacrol [101]. These compounds protect against neuronal damage from hypoxia-induced proinflammatory cytokines such as IL-1β and TNF-α and caspase 3 activity by suppressing hypoxia inducible factor-1α (HIF-1α) expression [102]. Taken together, these studies show that rosmarinic acid from M. officinalis and its derivatives play a vital role in the mechanisms that underlie memory enhancing function by improving cholinergic activity.

Bottom Line: Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease.Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75(NTR) superfamily.We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Gachon University, No. 191, Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea.

ABSTRACT
Alzheimer's disease (AD), characterized by progressive dementia and deterioration of cognitive function, is an unsolved social and medical problem. Age, nutrition, and toxins are the most common causes of AD. However, currently no credible treatment is available for AD. Traditional herbs and phytochemicals may delay its onset and slow its progression and also allow recovery by targeting multiple pathological causes by antioxidative, anti-inflammatory, and antiamyloidogenic properties. They also regulate mitochondrial stress, apoptotic factors, free radical scavenging system, and neurotrophic factors. Neurotrophins such as BDNF, NGF, NT3, and NT4/5 play a vital role in neuronal and nonneuronal responses to AD. Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease. Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75(NTR) superfamily. We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection. Although these phytochemicals have attracted attention owing to their in vitro neurotrophin potentiating activity, their in vivo and clinical efficacy trials has yet to be established. Therefore, further research is necessary to prove the neuroprotective effects in preclinical models and in humans.

No MeSH data available.


Related in: MedlinePlus