The Role of Dietary Polyphenols on Adult Hippocampal Neurogenesis: Molecular Mechanisms and Behavioural Effects on Depression and Anxiety

Table 1

Effects of polyphenols, particularly green tea/epigallocatechin and curcumin, on different neurochemical and morphological aspects of the hippocampus. BB: blueberry; EGC: epigallocatechin; GT: green tea.

Reference	Polyphenol	Treatment	Model	Effect on hippocampus	Proposed molecular mechanism(s)
Xu et al. 2009 [53]	Curcumin	Curcumin (5, 10 and 20 mg/kg, p.o.) or imipramine (10 mg/kg, i.p.)	Sprague-Dawley rats	Curcumin prevented hippocampal dendritic remodeling under conditions of chronic stress	Normalizing corticosterone levels and downregulating pCaMKII and glutamate receptor levels
Fernández-Fernández et al. 2011 [54]	LMN diet (polyphenols and fatty acids)	Control or LMN diet for 5 months	Tg2576 male mice as a model of AD crossing them with 129S1/SvImJ females	Reduction of Aβ plaques in the hippocampus when administration of diet occurred before plaque formation	—
Joseph et al. 2010 [55]	Blueberry	HNCs treated with BB extract, BB fractions (e.g., proanthocyanidin, PAC) or control medium were exposed to dopamine (DA, 0.1 mM), amyloid beta (Aβ42, 25 μM) or lipopolysaccharide (LPS, 1 μg/mL)	NeuroPureTM E18 primary rat hippocampal cells	Results indicated that the degree of protection against deficits in Ca^2+recovery varied as a function of the stressor and was generally greater against Aβ42 and LPS than DA	Prevention of deficit in Ca^2+buffering, normalization of cyclic CREB, protein kinase Cγ (PKCγ) and increased expression of ERK
Narita et al. 2011 [56]	Grape seed extract (GSE: Koshu and Muscat Bailey)	50 mM glutamate for 30 min, in the presence or absence of various concentrations of GSEs	Hippocampal tissue isolated from newborn mice (C57/B6; P1)	Koshu: alleviated the acute inactivation of Erk1/2 and dendrite retraction in cultured hippocampal neurons exposed to a toxic concentration of glutamate (1.0 ng/ml); Muscat Bailey: no neuroprotective effect	High-affinity molecular targets
Fujishita et al. 2009 [57]	Grape seed extract (GSE, Koshu)	0, 1, 10, 30, 100 μg/mL for 24 h or 0, 1, 10, 30, 100 μg/mL for 2, 6, or 12 h.	Culture of hippocampal neurons and astrocytes	GSE upregulated (concentration (100 μg/mL) and time-dependently); various mRNAs for cytokines, particularly for interleukin-6 (IL-6)	GSE could protect neuronal cells from death by oxidative stress via upregulated IL-6 production in astrocytes
Assunção et al. 2011 [58]	Green tea/epigallocatechin	19 month-old rats were fed with GT since age of 12 Months	Wistar rats	GT treatment protected proteins and lipids against oxidation and prevented the increase of lipofuscin deposition	—
Assunção et al. 2010 [59]	Green tea	Rats fed with GT from 12 to 19 months of age versus controls aged 19 months	Wistar rats	GT increased CREB activation and the levels of BDNF and Bcl-2, but had no effect on activation of NF-κB subunits	Long-term GT ingestion improves antioxidant systems and activates CREB in the aging rat hippocampal formation, leading to neuroprotection mediated by downstream upregulation of BDNF and Bcl-2
Yin et al. 2008; [60]	Green tea/Epigallocatechin-3-gallate	Treatment by EGCG (10–50 μM)	Hippocampal neuronal culture; lead exposure	Lead exposure significantly inhibited the viability of neurons; treatment with EGCG effectively increased cell viability and decreased ROS formation	Free radical scavenging and antioxidative properties of EGCG
Xu et al. 2010; [61]	Green tea/epigallocatechin	GT polyphenols were administered orally to rats from 4 to 8 weeks after experimentally induced cerebral hypoperfusion (400 mg/kg per day or 100 mg/kg)	Wistar rats	Reduced lipid peroxidation and oxidative DNA damage after chronic cerebral hypoperfusion	Free radical scavenging and antioxidative properties of GT polyphenols