[Retracted] Natural Products for Neurodegeneration: Regulating Neurotrophic Signals

Table 1

Promising studies regarding neurotrophic signals modulating potential of phytochemicals against neurodegeneration.

Phytochemicals	Species/studied material	Experimental model	Dose	Therapeutic uses	Mechanisms	Induced Neurotrophins	References
Epigallocatechin-3-gallate	C57BL/6 mice	Sevoflurane-induced neurotoxicity	25, 50, or 75 mg/kg	Neuroprotection	Activates CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathway	BDNF	[110]
	Rats	Acrylamide-induced neurotoxicity	10 mg/kg	Neuroprotection	Enhances acetylcholinesterase activity and reduces the expression of iNOS and COX-2 level	BDNF	[111]
	Sprague–Dawley rats	Spinal cord injury	10 and 20 mg/kg	Neuroprotection	Upregulation of BDNF and GDNF	BDNF, GDNF	[112]
	PC12 cells	Oxidative-radical-stress-induced apoptosis	0, 50, 100, 150 or, 200 μM	Neurodegenerative disorders	Activates PI3K/Akt and inhibits GSK-3	NGF	[113]
Curcumin	Rats	Stress-induced damage to hippocampal neurons	5, 10, and 20 mg/kg	Enhances hippocampal neurogenesis	Upregulation of 5-HT(1A) receptors and BDNF	BDNF	[80].
	Male Sprague–Dawley (SD) rats	6-OHDA-induced Parkinson’s disease	5, 10, and 20 mg/kg	Neural regeneration and neuroprotection	Activates Trk/PI3K signaling pathways	BDNF	[71]
	C57BL mice	MPTP-induced mice	0.5% or 2.0% (w/w)	Neuroprotective effect	Increases expression of GDNF and TGFβ1	GDNF	[114]
	Rats	Aβ-induced cognitive impairments	50 and 2.5 mg/kg	Improves cognitive deficit and neuroprotection	Activates PI3K/Akt signaling pathways and inhibits GSK-3	BDNF	[115]
	Adult and aged mice	D-galactose-induced	300 mg/kg	Improves cognitive impairment	Activates CREB signaling in the hippocampal dentate gyrus	BDNF	[116]
	Rodent cortical neurons		5 and 10 μM	Neuroprotection	Mediates through BDNF/TrkB-MAPK/PI-3 K-CREB signaling pathway	BDNF	[63]
Resveratrol	Adult Wistar rats	Two-vessel occlusion	20 mg/kg	Neuritogenesis, neuroinflammation, and neuroprotection	Activates ERK-mediated CREB regulation, induces BDNF, NGF, and GDNF secretion, and inhibits IL10, IL-1β, and NF-κB levels	BDNF and NGF	[117]
	Female Wistar rats	Dopaminergic neurons	25–100 μM	Produces neurotrophic effects	Promotes the release of neurotrophic factors	BDNF and GDNF	[118]
	Female Wistar rats	Astroglia-enriched cultures	25-100 μmmol/L	Neurological diseases	Induces the phosphorylation of (ERK1/2) andCREB in astroglia	BDNF and GDNF	[119].
	Male Wistar rats	Chronic unpredictable mild stress-induced behavioral abnormalities	20, 40 and 80 mg/kg	Antidepressant-like effects	Upregulates pERK, pCREB, and BDNF levels in the hippocampus and amygdala	BDNF	[120]
	Male Wistar rats	Phenylephrine-induced contraction of vascular smooth muscle cells	10 mg/kg	Neuroprotection	Increases BDNF serum concentrations and reduces the contractility of resistance arteries via NOS-3-independent mechanisms	BDNF	[121]
Quercetin	Male Chinese; Kunming mice	High-fat diet	8.5 and 17 mg/kg	Improves cognitive impairment	Modulates PI3K/AKT/Nrf2 pathway and activates CREB pathway	BDNF	[122]
	Adult male Sprague Dawley rat	Hypobaric hypoxia-induced memory deficit	50, 75 or 100 mg/kg	Ameliorates cognitive impairment	Regulates the expression of sirtuin 1, PGC-1α, and the proteins related with mitochondrial biogenesis and dynamics	BDNF	[123].
	Male Wistar albino rats	Streptozotocin-induced diabetes model	50 mg/kg	Neuroprotection	Akt survival pathway, enhances the level of TrkB and Bcl-2, and reduces the level of both cytochrome c and caspase-3	BDNF and NGF	[124]
	Adult male albino rats	Polychlorinated biphenyls-induced neurotoxicity	50 mg/kg	Protects and prevents neuronal damage	Prevents transmembrane tight junctional proteins and cytoplasmic accessory tight junctional proteins in the hippocampus and keeps the level of estradiol	BDNF	[125]
Daidzein	H19-7/IGF-IR neural cell line		20 nM -2000 nM	Neuroprotection	Blocks a selective Trk receptors inhibitor, K252a	BDNF	[126]
Alpinetin, luteolin, calycosin, isohamnerin	Primary rat astrocytes		10 μM	Improves neurodegenerative diseases	Triggers estrogen signaling	BDNF, GDNF and NGF	[85]
Ginkgolide B	Cultured hippocampal neurons	Aβ25–35-induced apoptosis	40 μg/ml	Neuroprotection	Upregulates BDNF	BDNF	[127]
Naringin	Sprague-Dawley rats	Spinal cord injury	20 and 40 mg/kg	Neuroprotection	Upregulates BDNF and VEGF and the inhibits the neural apoptosis	BDNF and VEGF	[128]
Genistein	Primary rat astrocytes		10 μM	Improves neurodegenerative diseases	Triggers estrogen signaling	BDNF, GDNF and NGF	[85]
	H19-7/IGF-IR neural cell line		20 nM -2000 nM	Neuroprotection	Blocks a selective Trk receptors inhibitor, K252a	BDNF	[126]
Butein, fisetin	Mice	Glutamate-induced neurotoxicity	40 mg/kg	Enhances cognitive effects	Inhibits iNOS and COX-2 and reactivates CREB-BDNF pathway	BDNF	[129]
Apigenin	Mice	MPTP-induced Parkinson’s disease mice	5, 10 and 20 mg/kg	Treatment of Parkinson’s disease	Reduces oxidative damage, neuroinflammation, and microglial activation	BDNF	[130]
Epicatechin	Male C57BL/6 J mice	Hippocampus of anxiety mice	4 mg/day	Treatment of mood disorders	Modulates monoaminergic and neurotrophic systems	BDNF	[131]
Rosmarinic acid	Sprague-Dawley rats	Chronic unpredictable stress	10 mg/kg	Improves depressive-like behaviors	Alters in ERK1/2 signaling	BDNF	[132]
Baicalein	Mice	Chronic unpredictable mild stress	1, 2, and 4 mg/kg	Treatment of depression	Triggers ERK-mediated neurotrophic action	BDNF	[133].
Ferulic acid	Mice	Corticosterone-induced	50, 100, or 250 mg/kg	Treatment of mood disorders	Increases CREB phosphorylation and BDNF mRNA level in the hippocampus	BDNF	[134].