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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: Berberine, an isoquinoline alkaloid, is the major component of Coptis chinensis. This plant belongs to the Ranunculaceae family and is used as a herbal medicine to treat skin inflammation, diarrhea, liver disease, and microbial infection in China [161, 162]. Various studies using neurodegenerative disease models have reported that berberine possesses multiple neuroprotective effects including neurotrophin-mediated neuroprotection. It has previously been reported that berberine (Figure 20) attenuates diabetic neuropathy in neuroblastoma cells by inducing hemeoxygenase-1 and NGF expression. ROS levels decreased, and NGF mediated neurite outgrowth increased via the PI3K/Akt/Nrf2-dependent pathway. Similar signaling pathways were shown to play a role in the inhibition of H2O2-induced neurotoxicity [77]. Berberine isolated from methanol extract of Coptidis rhizoma potentiated NGF-induced neurite outgrowth in PC12 cells and inhibited acetylcholinesterase activity as compared to physostigmine [163]. In another study, berberine significantly decreased the expression of the proinflammatory cytokines Cox-2, IL-1β, and TNF-α and markedly restored levels of BDNF and CREB and reduced the escape latency in rats with scopolamine-induced memory impairments [164]. Berberine pretreatment prevents Aβ-induced IL-6 and MCP-1 production and downregulated Cox-2 and iNOS expression in primary microglia and BV2 cells. This was achieved through activation of AKT/ERK1/2-mediated phosphorylation of IκB-α and NF-κB and not stimulation of the JNK pathway [165].


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: Berberine, an isoquinoline alkaloid, is the major component of Coptis chinensis. This plant belongs to the Ranunculaceae family and is used as a herbal medicine to treat skin inflammation, diarrhea, liver disease, and microbial infection in China [161, 162]. Various studies using neurodegenerative disease models have reported that berberine possesses multiple neuroprotective effects including neurotrophin-mediated neuroprotection. It has previously been reported that berberine (Figure 20) attenuates diabetic neuropathy in neuroblastoma cells by inducing hemeoxygenase-1 and NGF expression. ROS levels decreased, and NGF mediated neurite outgrowth increased via the PI3K/Akt/Nrf2-dependent pathway. Similar signaling pathways were shown to play a role in the inhibition of H2O2-induced neurotoxicity [77]. Berberine isolated from methanol extract of Coptidis rhizoma potentiated NGF-induced neurite outgrowth in PC12 cells and inhibited acetylcholinesterase activity as compared to physostigmine [163]. In another study, berberine significantly decreased the expression of the proinflammatory cytokines Cox-2, IL-1β, and TNF-α and markedly restored levels of BDNF and CREB and reduced the escape latency in rats with scopolamine-induced memory impairments [164]. Berberine pretreatment prevents Aβ-induced IL-6 and MCP-1 production and downregulated Cox-2 and iNOS expression in primary microglia and BV2 cells. This was achieved through activation of AKT/ERK1/2-mediated phosphorylation of IκB-α and NF-κB and not stimulation of the JNK pathway [165].

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