An insight into the neuroprotective effects and molecular targets of pomegranate ( Punica granatum ) against Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that still has no permanent cure. The drugs prescribed in the present days are only for symptomatic relief for the patients. Many studies correlating the reduction in the incidence of AD with the diet consumed have been published. These studies showed that a diet rich in polyphenols is associated with a decrease in the incidence of AD. The present review is focused on the ability of pomegranate and its bioactive components to ameliorate the progression of AD and their ability to exert a neuroprotective effect. Various studies showing the ability of pomegranate in inhibiting enzymes, reducing reactive oxygen species, inhibition of microglial activation, inhibition of tau protein hyperphosphorylation, maintenance of synaptic plasticity, anti-inflammatory activity and its ability to inhibit Beta secretase-1 (BACE-1) has been reviewed in this article. In spite of the lack of studies on humans, there are compelling evidence indicating that pomegranate can reduce various risk factors involved in the causation of AD and thus can be used as a persistent nutraceutical to slow ageing and for providing neuroprotection for the treatment of AD. Abbreviations: ACh, Acetylcholine; AChE, Acetylcholinesterase; AD, Alzheimer's disease; AGEs, Advanced Glycation End products; APP, Amyloid precursor protein; Aβ, Amyloid-beta; BACE, Beta secretase or β-site amyloid precursor protein cleaving enzyme; BBB, Blood brain barrier; BDNF, Brain derived neurotrophic factor; BuChE, Butyrylcholinesterase; CAM, Chick Chorioallantoic Membrane; COVID 19, Corona virus disease 19; COX, Cyclooxygenase; DPPH, 2,2 diphenyl picryl hydrazyl; ER, Endoplasmic Reticulum; FAO, Food and Agriculture organization; FDA, Food and drug administration; GFAP, Glial-fibrillar acidic protein; GPx, Glutathione peroxidase; GSH, Glutathione; GST, Glutathione S transferase; HFD, High-fat diet; IL-6, Interleukin-6; LDH, Lactate dehydrogenase; LO, Lipooxygenase; LPS, Lipopolysaccharide; MAO, Mono amine oxidase; MDA, Malondialdehyde; MedDi, Mediterranean diet; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; mTOR, Mammalian Target of Rapamycin; NAD, Nicotinamide adenine dinucleotide; NFAT, Nuclear factor of activated T-cells; NO, Nitric oxide; NQO1, Quinone oxidoreductase 1; Nrf2, Nuclear factor erythroid 2-related factor 2; oAβ, Oligomeric amyloid-beta; pCREB, Cyclic AMP-Response Element Binding Protein; PGE2, Prostaglandin E2; RON, Reactive nitrogen species; ROS, Reactive oxygen species; SOD, Superoxide dismutase; STZ, Streptozotocin; TNF-α, Tumor necrosis factor α; UNESCO, The United Nations Educational, Scientific and Cultural Organization; WHO, World Health Organization.