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Cited by 212Medicinal Plants and NeuroprotectionAlzheimer's disease research and treatmentsNerve injury and regeneration

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Phytochemicals That Regulate Neurodegenerative Disease by Targeting Neurotrophins: A Comprehensive Review

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Venkatesan, Ramu, Ji, Eunhee, Kim, Sun Yeou·2015·BioMed Research International
DOI 10.1155/2015/814068PMC PMC4446472
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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.

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Crossref · 10.1155/2015/814068

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Figures

Figure 1 Schematic representation of phytochemicals involved with neurotrophins. By binding to the Trk receptor, neurotrophin signaling mediates cell survival, proliferation, and differentiation through the Ras/MAPK, PI3K/AKT, and PL-Cγ pathways. NGF-p75NTR receptor binding activates bidirectional cell survival and apoptosis via the NF-κB and JNK pathways, as well as external stress stimuli-mediated generation of ROS with suppression of antioxidative enzyme levels. Trk, tropomyosin-related kinase; p75NTR, p75 neurotrophin receptor; NGF, nerve growth factor; BDNF, brain derived neurotrophic factor; LPS, lipopolysaccharide; NADPH, nicotinamide adenine dinucleotide phosphate; PI3K, phosphatidylinsoitol-3-kinase; mTOR, mammalian target of rapamycin; MEK, mitogen-activated protein kinase; MAPK, mitogen activated protein kinase; ERK, extracellular signal-regulated kinases; PL-Cγ, phospholipase Cγ; PKC, protein kinase C; NF-κB, nuclear factor-kappa B; JNK, c-Jun N-terminal kinase; IκB, inhibitory kappa B; CREB, cyclic adenosine monophosphate response element binding protein; GSK3β, glucose synthase kinase-3β; CaMKII/IV, Ca2+-calmodulin kinase II/IV. 1: Diosniposide B, 2: Diosgenin, 3: Cyanidin-3-glucopyranoside, 4: 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene, 5: Spicatoside A, 6: Quercetin, 7: Apigenin, 8: Ginsenoside Rg3, 9: Rosmarinic acid, 10: Ginkgolide B, 11: Limonoid, 12: 4,6-dimethoxy phenanthrene-2,3,7-triol, 13: Furostanol, 14: Coreajaponins B, 15: Quinic acid, 16: Luteolin-7-O-β-glucopyranoside, 17: Kaempferol, 18: (−)-4,5-dicaffeoyl quinic acid, 19: (−)-3,5-dicaffeoyl mucoquinic acid, 20: (−)-3,4-dicaffeoyl mucoquinic acid, 21: Ginsenosides, 22: Panaxynol, 23: Nigranoic acid, 24: Clerodane diterpenoids, 25: Ligraminol E4-O-β-d-xyloside, 26: Geniposidic acid, 27: Epigallocatechin-3-galate, 28: Curcumin, 29: Resveratrol, 30: Berberine, 31: 6-shogaol, 32: Oleuropein, 33: Honokiol and magnolol, 34: Huperzine A.
Figure 1 Schematic representation of phytochemicals involved with neurotrophins. By binding to the Trk receptor, neurotrophin signaling mediates cell survival, proliferation, and differentiation through the Ras/MAPK, PI3K/AKT, and PL-Cγ pathways. NGF-p75NTR receptor binding activates bidirectional cell survival and apoptosis via the NF-κB and JNK pathways, as well as external stress stimuli-mediated generation of ROS with suppression of antioxidative enzyme levels. Trk, tropomyosin-related kinase; p75NTR, p75 neurotrophin receptor; NGF, nerve growth factor; BDNF, brain derived neurotrophic factor; LPS, lipopolysaccharide; NADPH, nicotinamide adenine dinucleotide phosphate; PI3K, phosphatidylinsoitol-3-kinase; mTOR, mammalian target of rapamycin; MEK, mitogen-activated protein kinase; MAPK, mitogen activated protein kinase; ERK, extracellular signal-regulated kinases; PL-Cγ, phospholipase Cγ; PKC, protein kinase C; NF-κB, nuclear factor-kappa B; JNK, c-Jun N-terminal kinase; IκB, inhibitory kappa B; CREB, cyclic adenosine monophosphate response element binding protein; GSK3β, glucose synthase kinase-3β; CaMKII/IV, Ca2+-calmodulin kinase II/IV. 1: Diosniposide B, 2: Diosgenin, 3: Cyanidin-3-glucopyranoside, 4: 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene, 5: Spicatoside A, 6: Quercetin, 7: Apigenin, 8: Ginsenoside Rg3, 9: Rosmarinic acid, 10: Ginkgolide B, 11: Limonoid, 12: 4,6-dimethoxy phenanthrene-2,3,7-triol, 13: Furostanol, 14: Coreajaponins B, 15: Quinic acid, 16: Luteolin-7-O-β-glucopyranoside, 17: Kaempferol, 18: (−)-4,5-dicaffeoyl quinic acid, 19: (−)-3,5-dicaffeoyl mucoquinic acid, 20: (−)-3,4-dicaffeoyl mucoquinic acid, 21: Ginsenosides, 22: Panaxynol, 23: Nigranoic acid, 24: Clerodane diterpenoids, 25: Ligraminol E4-O-β-d-xyloside, 26: Geniposidic acid, 27: Epigallocatechin-3-galate, 28: Curcumin, 29: Resveratrol, 30: Berberine, 31: 6-shogaol, 32: Oleuropein, 33: Honokiol and magnolol, 34: Huperzine A.CC BY · PubMed Central
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Research works printed but not linked: 8

  1. 1992, The Canadian Journal of Neurological Sciences, 19, 103
  2. 1992, Human Genetics, 89, 365
  3. 1982, Advances in Neurology, 36, 281
  4. 2014, Natural Product Communications, 9, 703
  5. 10.3760/cma.j.issn.0366-6999.2011.17.012 · DOI
  6. 2007, Asia Pacific Journal of Clinical Nutrition, 16, 43
  7. 2012, Zhongguo Ying Yong Sheng Li Xue Za Zhi, 28, 467
  8. 10.1016/j.cbi.2005.09.003 · DOI

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Metadata

Authors
Venkatesan, R., Ji, E., & Kim, S. Y.
Affiliations
Gachon University (KR)
Corresponding author
Kim, Sun Yeou
ORCID
Venue
BioMed Research International
Publisher
Wiley
Published
2015
Volume
2015
Pages
1-22
ISSN
  • 1110-7243 (ISSN-L)
  • 2314-6133
  • 2314-6141
DOI
10.1155/2015/814068
PMC
PMC4446472
OpenAlex
W2136484866
Cited by
212
References
174
Citations by year
2026: 21 · 2025: 35 · 2024: 15 · 2023: 23 · 2022: 14 · 2021: 21 · 2020: 12 · 2019: 15 · 2018: 17 · 2017: 18 · 2016: 17 · 2015: 4
FWCI
4.47
Type
journal article
Language
en
Open access
Licence
Locations
  • BioMed Research International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Korean government (NRF-2014M3A9B6069338)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords
Alzheimer's disease, phytochemicals, neurotrophins, neuroprotection, Trk receptors, p75 neurotrophin receptor, brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, iridoid glycosides, terpenoids, alkaloids, steroidal saponins, phenolic compounds, neurodegenerative diseases, mitochondrial stress, apoptosis, oxidative stress, anti-inflammatory activity
MeSH terms
Alzheimer Disease, Animals, Humans, Phytotherapy, Plants, Medicinal, Polysaccharides, Plant Preparations

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