TABLE 5.

Phytochemicals that modify neurotrophic factor signaling

Phytochemical	Target Tissue/Cells	Effects	Involved Molecular Mechanism	Reference
Rutin	Frontal cortex of rat brain	Neuroprotective effects against neurotoxicity of Aβ	Increased BDNF, pCREB	Moghbelinejad et al. (2014)
Curcumin	Hippocampus and frontal cortex	Effects on the neurotrophin factor expression	Increased BDNF, pCREB	Xu et al. (2006b)
	β-amyloid–induced rats	Prevent behavioral impairments, neuroinflammation, and τ hyperphosphorylation	Increased BDNF and Akt/GSK-3β	Hoppe et al. (2013)
	TNFR1 and TNFR2 double knockout mice	Protect cultured neurons against glutamate-induced excitotoxicity by TNFR2 activation	Increased BDNF	Kawamoto et al. (2013)
		Increase levels of phosphor-ERK and Akt	Increased BDNF, pCREB	Wang et al. (2010c)
Resveratrol	Prefrontal cortex and hippocampus	Effective in promoting astroglia-derived neurotrophic factor release	Increased BDNF, GDNF	Zhang et al. (2012a)
	Hippocampus of prenatally stressed rat	Improve the expression of DCX-positive neuron	Increased BDNF	Madhyastha et al. (2013)
	Hippocampus neural progenitor cells	Deficits in hippocampus-dependent spatial learning and memory	Decreased BDNF-pCREB signaling	Park et al. (2012a)
Ferulic acid	Hippocampus (CORT-treated mice and stress-induced depression-like behavior of mice)	Effects on the mood disorders such as depression	Increased BDNF mRNA	Yabe et al. (2010)
Lancemaside A	Hippocampus	Ameliorate memory and learning deficits	Increased BDNF, pCREB	Jung et al. (2012)
Heptamethoxyflavone	Hippocampus after ischemia	Induce BDNF production in astrocytes and enhance neurogenesis after brain ischemia	Increased BDNF, pCREB	Okuyama et al. (2012)
Oroxylin A	Primary cortical neuronal culture cell	Responsible for the neuroprotective or memory-enhancing effects	Increased BDNF expression	Jeon et al. (2011)
	Hippocampus	Attenuate the memory impairment and show neuroprotective effects	Increased BDNF, pCREB	Kim et al. (2006)
Procyanidins	Hippocampus and cerebral cortex	Enhance CREB-dependent transcription through the activation of ERK signaling pathway	Increased pCREB	Xu et al. (2010a)
Bilobalide and quercetin	Mice model of AD (hippocampus)	Increase cell proliferation in the hippocampal neurons/enhance neurogenesis and synaptogenesis	Increased pCREB	Tchantchou et al. (2009)
Catechin	Senescence-accelerated mouse prone-8 (hippocampus)	Prevent spatial learning and memory decline of SAMP8 mice by decreasing Aβ (1-42) oligomers and upregulating synaptic plasticity-related proteins	Increased BDNF, pCREB	Li et al. (2009)
Olive polyphenols	Hippocampus, olfactory, striatum, and frontal cortex	NGF and BDNF elevation in the hippocampus and olfactory bulbs and a decrease in the frontal cortex and striatum	Increased BDNF, NGF	De Nicoló et al. (2013)
C-dideoxyhexosyl flavones	PC12 cells	Neurite outgrowth enhancing activities	Increased NGF	Xu et al. (2013)
Baicalein	C17.2 cells hippocampus	Protect NPCs against irradiation-induced necrotic cell death and the spatial learning and memory retention deficits after whole-brain irradiation	Increased BDNF-pCREB signaling	Oh et al. (2013)
Diallyl disulfide	Hippocampus NPC	Decreased the proliferation of NPCs in the dentate gyrus adverse effects on hippocampal neurogenesis and neurocognitive functions	Decreased BDNF-pCREB signaling	Ji et al. (2013)

CORT, corticosterone; DCX, doublecortin; NPC, neural progenitor cell; pCREB, phosphorylated CREB; TNFR, tumor necrosis factor receptor.