Naringenin protects AlCl3/D-galactose induced neurotoxicity in rat model of AD via attenuation of acetylcholinesterase levels and inhibition of oxidative stress

Abstract

Currently prescribed medications for the treatment of Alzheimer's disease (AD) that are based on acetylcholinesterase inhibition only offer symptomatic relief but do not provide protection against neurodegeneration. There appear to be an intense need for the development of therapeutic strategies that not only improve brain functions but also prevent neurodegeneration. The oxidative stress is one of the main causative factors of AD. Various antioxidants are being investigated to prevent neurodegeneration in AD. The objective of this study was to investigate the neuroprotective effects of naringenin (NAR) against AlCl 3 +D-gal induced AD-like symptoms in an animal model. Rats were orally pre-treated with NAR (50 mg/kg) for two weeks and then exposed to AlCl 3 +D-gal (150 mg/kg + 300 mg/kg) intraperitoneally for one week to develop AD-like symptoms. The standard drug, donepezil (DPZ) was used as a stimulator of cholinergic activity. Our results showed that NAR pre-treatment significantly protected AD-like behavioral disturbances in rats. In DPZ group, rats showed improved cognitive and cholinergic functions but the neuropsychiatric functions were not completely improved and showed marked histopathological alterations. However, NAR not only prevented AlCl 3 +D-gal induced AD-like symptoms but also significantly prevented neuropsychiatric dysfunctions in rats. Results of present study suggest that NAR may play a role in enhancing neuroprotective and cognition functions and it can potentially be considered as a neuroprotective compound for therapeutic management of AD in the future. PLOS ONE | https://doi.org/10.1371/journal.pone.0227631 January 16, 2020 1 / 30 OPEN ACCESS Citation: Haider S, Liaquat L, Ahmad S, Batool Z, Siddiqui RA, Tabassum S, et al. (2020) Naringenin protects AlCl 3 /D-galactose induced neurotoxicity in rat model of AD via attenuation of acetylcholinesterase levels and inhibition of oxidative stress. PLoS ONE 15(1): e0227631.

Bay Leaf (Laurus Nobilis L.) Incense Improved Scopolamine-Induced Amnesic Rats by Restoring Cholinergic Dysfunction and Brain Antioxidant Status

“…The preference of novelty in rodents and the memory abilities were detected by a novel object recognition (NOR) task according to a method described previously by Foyet et al [31]. The preference of a novel object may indicate the existence of familiar object presentation in the memory of a rat [32].…”

Cognitive Facilitation and Antioxidant Effects of an Essential Oil Mix on Scopolamine-Induced Amnesia in Rats: Molecular Modeling of In Vitro and In Vivo Approaches

“…The results suggested that MO exhibits neuroprotective effects against oxidative stress. Haider et al [34] reported that naringenin, a flavonoid from C. aurantium, protects AlCl 3 /D-galactose-induced neurotoxicity in a rat model of AD via attenuation of AChE levels and inhibition of oxidative stress. Nobiletin, from C. lemon peel, was found to be a potent candidate for the prevention of AD through the inhibition of oxidative stress, apoptosis, and inflammation via suppression of interleukin-1β, tumor necrosis factor-α, nitric oxide (NO), and prostaglandin E2 production in response to Aβ 25-35 stimulation [35].…”

“…Novel object recognition (NOR) has been extensively used for determining alterations in cognitive functions as it can measure the preference of novelty in rodents. The preference of a novel object may indicate the existence of familiar object presentation in the memory of a rat [34]. Rats were trained and tested in a NOR test, as previously described by Foyet et al [51].…”

Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals

“…Naringenin protects Aβ 25-35 -caused damage via ER and PI3K/Akt-Mediated Pathways [49,52]. Naringenin also protects AlCl 3 /D-galactose-induced neurotoxicity in the rat model of AD via inhibition of attenuation of acetylcholinesterase levels and attenuation of oxidative stress [53]. A new study suggested the therapeutic effects of piperine against oxidative insult, neuroinflammation, and neurochemical changes induced by ICV-STZ infusion in mice [54].…”