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

Table 1

Plant-derived phytochemicals that affect neurotrophins.

Plant source	Phytochemicals	Pharmacological effects	Medicinal use	Reference
Aster scaber	(−)-3,5-Dicaffeoylmucoquinic acid, quinic acid	Activates Trk/ERK1/2/PI3K-mediated neuritogenesis, increases SOD, and reduces MDA activity, neurotrophic mimetic action	Neurodegenerative disease, neuroinflammation, neuritogenesis, and neuroprotection	[52]
Abies holophylla	Ligraminol E4-O-β-d-xyloside, (8R,9S,7′S,8′R)-4,4′,7′-trihydroxy-3,3′,9-trimethoxy-9,9′-epoxylignan, juniperigiside	Inhibits NO production and activates Trk-mediated NGF production	Neurodegenerative disease, neuropathy, neuritogenesis, and neuroinflammatory	[75]
Camellia sinensis	Epigallocatechin-3-galate	Activates Trk signaling pathway-mediated neurite outgrowth, PI3K/AKT/GSK-3β, induces NGF, BDNF secretion, and inhibits cas3 and ROS level	Neuritogenesis, neuroinflammation, neuroprotection, and cognitive deficit	[76]
Coptis chinensis	Berberine	Activates AKT/GSK-3β/Nrf2-mediated regulation, cholinergic activity-mediated neurite outgrowth, induces NGF and BDNF secretion, and inhibits Cox2, TNF-α, NF-B, IL-1β, and iNOS levels	Neuritogenesis, neuroinflammation, and neuroprotection	[77]
Curcuma longa	Curcumin	Activates PKC/ERK-mediated CREB regulation and AKT/GSK-3β mediated regulation, induces BDNF secretion, and inhibits Cas3, TNF-α, and NF-B levels	Neuritogenesis, neuroinflammation, and neuroprotection	[78]
Dioscorea nipponica	Diosniposide B, 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene, sapogenin	Activates Trk signaling pathway-mediated neurite outgrowth and induces NGF secretion, inhibits NO	Neuritogenesis, neuroinflammation, and neuroprotection	[18]
Eucommia ulmoides	Geniposidic acid	Activates PI3K/AKT, p38 MAPK/ERK1/2-mediated inhibition of LDH, PARP, cleaved caspase 3, MMPs and cytochrome C with increase in Bcl-2, Bcl-xL, BDNF expression, and AChE inhibition	Anti-apoptotic, Alzheimer’s disease, neurodegenerative disease, and neuroprotection	[79]
Ginkgo biloba (L)	Ginkgolide B	Activates Trk/Ras/MAPK-mediated neurite outgrowth, induces BDNF secretion, and reduces ROS, LDH, caspase3, and proapoptotic factors	Antidepressant, dementia, neuroprotective, nootropic, phosphodiesterase inhibitor, antioxidant, neuritogenesis, and neuroinflammation	[80]
Huperzia serrata	Huperzine A	Activates Trk/MAPK/ERK-mediated neurite outgrowth, induces NGF and BDNF secretion, reduces AChE, TNF-α, NF-B, IL-1β, and MDA levels, and increases SOD, GSH-Px, Cat, Bcl-2, Bcl-xL, and TGF-β level	Neuritogenesis, neuroinflammation, and neuroprotection	[81]
Liriope platyphylla	Spicatoside A	Activates Trk, ERK1/2/PI3K-mediated neurite outgrowth and induces NGF and BDNF secretion	Neurodegenerative disease, neuritogenesis, and neuroprotection	[35]
Magnolia officinalis	Honokiol, magnolol	Induces NGF and BDNF secretion, inhibits TNF-α, NF-B, IL-1β, IL-6, and ROS levels, and increases Akt activity	Neuritogenesis, neuroinflammation, and neuroprotection	[82]
Melissa officinalis (L)	Rosmarinic acid, neral/geranial, citronellal, isomenthone, ε-caryophyllene, ursolic acid	NGF mimetic, activates ERK1/2-mediated neurite outgrowth, improves cholinergic activity and NF-B pathway, and inhibits IL-1β, TNF-α, and caspase 3	Antidepressant, cognitive disorders, neuritogenesis, neuroinflammation, and neuroprotection	[83]
Melia toosendan	Limonoid, 1α,3α-dihydroxyl-7α-tigloyloxy-12α-ethoxylnimbolinin & 12-O-ethyl-1-deacetyl-nimbolinin B	Activates PKA/ERK1/2-mediated neurite outgrowth, induces NGF secretion, and decreases LDH activity	Neurodegenerative disease, neuropathy, neuritogenesis, neuroprotective, and neuroinflammatory	[84]
Morus alba (L)	Quercetin, cyanidin-3-O-β-glucopyranoside, gallic acid	Induces PI3K/ERK1/2-mediated CREB activation, neurite outgrowth, and NGF secretion	Cognitive disorders, antiaging, neuritogenesis, and neuroprotection	[85, 86]
Olea europaea	Oleuropein	Induces NGF and BDNF secretion and increases GSH level	Neuroprotection and neuroinflammation	[87]
Passiflora edulis (L)	Apigenin-8-C-β-digitoxopyranoside, apigenin- 8-C-β-boivinopyranoside, luteolin-8-C-β-boivinopyranoside	Inhibits NO, iNOS, PGE2-mediated modulation of ERK 1/2, p38 MAPK, JNK, and BDNF-induced neurite outgrowth	Neuritogenesis, anxiolytic, neuroinflammation, and neuroprotection	[88]
Panax ginseng	Ginsenoside Rg3, panaxynol	Activates cAMP/MAPK & Trk-mediated neuritogenesis, TNF-α, NF-B, IL-1β, iNOS, neurotrophic mimetic action	Neuroinflammation, neurodegenerative disease, neuroprotection, and neuritogenesis	[89]
Pimpinella brachycarpa	3,5-O-trans-dicaffeoylquinic acid methyl ester, 1-O-trans-p-coumaroyl-5-O-cis-p-coumaroylquinic  acid	Inhibits NO, iNOS production, and boost antioxidant system	Neuroinflammation	[52]
Ptychopetalum olacoides	6α,7α-Dihydroxyannonene, 7α,20-dihydroxyannonene, clerodane diterpenoid	Neurotrophic mimetic action and mediates neurite outgrowth	Neurodegenerative disease, neuritogenesis, and neuroprotection	[90]
Schisandra chinensis	α-Iso-cubebene, dibenzocyclooctadiene lignans, schisanchinins A-D, nigranoic acid	Activates PKA/B/Ca^2+-CaMKII/ERk1/2-mediated CREB and Nrf2 pathway activation, induces BDNF and c-fos expression, and inhibits NO and PGE2 production	Parkinson’s disease, neuroinflammation, and neuroprotection	[91]
Vitis vinifera	Resveratrol	Activates ERK-mediated CREB regulation, induces NGF, GDNF, and BDNF secretion, and inhibits caspase3, TNF-α, NF-B, IL10, IL-1β, MCP1, and MDA levels, increases SOD level.	Neuritogenesis, neuroinflammation, and neuroprotection	[92]
Zingiber officinale	6-shogaol	Activates Trk-mediated neurite outgrowth, induces NGF, BDNF, and GDNF secretion, inhibits Cox2, TNF-α, NF-B, IL-1β, NO, p38, iNOS, Bax, PG-E2, and ROS level, and increases SOD, Bcl-2, and Bcl-xL levels	Neuritogenesis, neuroinflammation, and neuroprotection	[93]