Table 3.
Summary of the main in vivo and in vitro findings related to the effect of the pomegranate intake on memory and neuro-inflammation implicated in Alzheimer’s disease.
| Animal Model/ Cell Line/CTI |
Induction of Neuro-Inflammation | Pomegranate Part or Product | Dose and Period of Treatment | Findings | Ref |
|---|---|---|---|---|---|
| Animal studies | |||||
| Male C57BI/6 mice | Chronic injection of Aβ peptide |
Pomegranate peel extract | 800 mg/kg/day for 35 days |
Improves spatial memory, and the expression of neurotrophin BDNF; reduce amyloid plaque density, AchE activity, lipid peroxidation and TNF-α level; no hepatic lesions. | [89] |
| Male ICR mice | LPS injection (250 µg/kg) | Punicalagin | 1.5 mg/kg for 4 weeks |
Memory improvement; no effect on swimming speed; reduction of BACE1 expression and Aβ 1-42 generation; no effect on APP expression; decrease the Il-1-β, IL-6 and TNF-α, H2O2 and MDA level; increase GSH/GSSG ratio; inhibition of iNOS and Co-2 activities; decrease NF-kB DNA binding activity; suppress IkB-α phosphorylation and P50 and P65 subunits translocation. | [6] |
| APPsw/Tg2576 mice | Experimental animal model overexpressing APP | Pomegranate fruit | 4% w/w, for 15 months | Decrease serum concentration of IL-2, IL-3, IL-4, IL-5, IL-9, IL-10, and Eotaxin; decrease the level of IL-1β, TNF-α, and IL-6, Aβ1–42 and 40, both in the cortex and hippocampus areas. | [3] |
| APPsw/Tg2576 mice | Transgenic female | Pomegranate extract | 4% w/w, for 15 months | Significant inhibition of TNF-α, Il-1-β, iNOS, ccl2, and Il-10 genes expression. | [90] |
| APP/PS1 transgenic mice | Transgenic female | Urolithin A | 300 mg/kg, for 14 days | Neuronal death attenuation; hippocampal neurogenesis improvement; diminished astrocytes and microglia activation; reduction in the level of IL-1β, IL-6, and TNF-α. | [94] |
| In vitro studies | |||||
| The human neuroblastoma (SK-N-SH) cells | IL-1 β (10 U/mL) | Standardized Pomegranate fruit juice (skins) | 25–200 μg/mL, for 24 h |
Inhibition of Co-2 activity, and PGE-2 production; significant inhibition of IκB and IKK phosphorylation; reduction of BACE1 gene expression and Aβ production. | [8] |
| HEK293 cells | TNFα (1 ng/mL) | 25–200 μg/mL, for 6 h | Significant inhibition of NF-κB transactivation. | ||
| Primary astrocyte and microglial BV-2 cells | LPS-(10, 20 and 50 µM), for 1 h | Punicalagin | (1 µg/mL), for 24h | Suppress the activation of NF-kB; inhibit IkB degradation and p50 and p65 translocation; inhibit APP and BACE1 transcription. | [6] |
| Microglial BV-2 cell | LPS | Pomegranate seed oil | 25 μg/mL, for 24h | Slight inhibition of TNF-α and iNOS gene expression; prevent microglia cells apoptosis. | [92] |
| Clinical trials | |||||
| NCT02093130 | _ | Pomegranate juice | 236.5 mL, for 12 months | Pomegranate juice supplementation stabilizes human capacities in terms of the acquisition of new visual information during advancement with age. | [93] |
CTI: clinical trial identifier; BDNF: brain-derived neurotrophic factor; TNF-α: tumor necrosis factor-alpha; Aβ1-42: amyloid beta 1-42; BACE1: beta-site APP cleaving enzyme 1; APP: Amyloid precursor protein; IL-1β: interleukin-1β; IL-6: interleukin-6; H2O2: hydrogen peroxide; MDA: malondialdehyde; GSH: reduced glutathione; GSSG: oxidized glutathione; iNOS: inducible nitric oxide synthase; Co-2: cyclooxygenase 2; AchE: acetylcholinesterase; NF-κB: nuclear factor-kappa B; IkB: inhibitor of nuclear factor-κB; P50: p50 protein; P65: p 65 protein; IL-2: interleukin-2; IL-3: interleukin-3; IL-4: interleukin-4; IL-5: interleukin-5; IL-9: interleukin-9; IL-10: interleukin-10; PGE-2: prostaglandin-2; IKK: inhibitor of nuclear factor-κB kinase; SK-N-SH: human neuroblastoma cell line. BV-2: murine microglial cell line; HEK293: human embryonic kidney cells-293; Ccl2: chemokine ligand 2; LPS: Lipopolysaccharide.