Ellagic acid attenuates enhanced acetylcholinesterase reactivity in an experimental model of Alzheimer′s disease induced by beta amyloid25-35 in the rat

Document Type : Research Paper


1 Shahed Univ.

2 shahed


Background and Objective: Alzheimer’s disease (AD) is a multifactorial disease with debilitating consequences and few therapeutic strategies exist for it. With regard to antioxidant capacity and anti-β-amyloid polymerization potential of ellagic acid, this study was conducted to evaluate the effect of this substance on enhanced acetylcholinesterase reactivity in an experimental model of Alzheimer′s disease induced by beta amyloid25-35 in the rat.
Materials and Methods: In this experimental study, 32 male Wistar rats were divided into 4 equal groups, i.e. sham, treated-sham, Alzheimeric, and treated-Alzheimeric. For induction of AD, 2 µl of β-amyloid 25-35 (10 µg/2 µl) was microinjected bilaterally into CA1 of the dorsal hippocampus. The daily treatment with ellagic acid was done for one week at a dose of 10 mg/kg (i.p.) till 1 h pre-surgery. At third week after surgery, histochemistry for acetylcholinesterase reactivity was performed.
Results: Alzheimeric group showed enhanced reactivity for acetylcholinesterase in dorsal hippocampus that was significant as compared to sham group (pConclusion: Pretreatment of beta amyloid-induced-Alzheimeric rats by ellagic acid could ameliorate acetylcholinesterase reactivity in the dorsal hippocampus and this could possibly improve memory deterioration in AD.


1.   Querfurth HW, LaFerla FM. Alzheimer's Disease. New England Journal of Medicine 2010;362(4):329-44.
2.   Bernal-Mondragon C, Rivas-Arancibia S, Kendrick KM, Guevara-Guzman R. Estradiol prevents olfactory dysfunction induced by A-beta 25-35 injection in hippocampus. BMC Neuroscience 2013;14:104.
3.   Anand R, Gill KD, Mahdi AA. Therapeutics of Alzheimer's disease: Past, present and future. Neuropharmacology 2014;76:27-50.
4.   Jurenka JS. Therapeutic applications of pomegranate (Punica granatum L.): a review. Alternative Medicine Review : A Journal of Clinical Therapeutic 2008;13(2):128-44.
5.   Uzar E, Alp H, Cevik MU, Firat U, Evliyaoglu O, Tufek A, et al. Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2012;33(3):567-74.
6.   Feng Y, Yang SG, Du XT, Zhang X, Sun XX, Zhao M, et al. Ellagic acid promotes Abeta42 fibrillization and inhibits Abeta42-induced neurotoxicity. Biochemical and Biophysical Research Communications 2009;390(4):1250-4.
7.   Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition: Elsevier Science & Technology Books 2007.
8.   Abe E, Casamenti F, Giovannelli L, Scali C, Pepeu G. Administration of amyloid beta-peptides into the medial septum of rats decreases acetylcholine release from hippocampus in vivo. Brain Research 1994;636(1):162-4.
9.   Emre M, Geula C, Ransil BJ, Mesulam MM. The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected beta-amyloid in the rat brain. Neurobiology of Aging 1992;13(5):553-9.
10. Harkany T, Lengyel Z, Soos K, Penke B, Luiten PG, Gulya K. Cholinotoxic effects of beta-amyloid (1-42) peptide on cortical projections of the rat nucleus basalis magnocellularis. Brain Research 1995;695(1):71-5.