Neuroprotective effect of naringin against cerebellar changes in Alzheimer’s disease through modulation of autophagy, oxidative stress and tau expression: An experimental study

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by gradual cognitive decline. Strong antioxidants that inhibit free radicals, such as polyphenols, reduce the likelihood of developing oxidative stress-related degenerative diseases such as AD. Naringin, a flavonoid found in citrus fruit shown to be neuroprotective, reduce oxidative damage and minimize histopathological changes caused by ischemic reperfusion, enhance the long-term memory in AD animal models. This work aimed to comprehend the role of naringin in the defense of the cerebellum against aluminum chloride (AlCl3)-induced AD in rats by investigating the behavioral, neurochemical, immunohistochemical, and molecular mechanisms that underpin its possible neuroprotective effects. Twenty-four adult albino rats were divided into four groups (n = 6/group): (i) Control (C) received saline per oral (p.o.), (ii) Naringin(N)-received naringin (100 mg/kg/d) p.o, (iii) AlCl3-recived AlCl3 (100 mg/kg/d) p.o and (iv) AlCl3 + Naringin (AlCl3 + N) received both AlCl3 and naringin p.o for 21 days. Behavioral tests showed an increase in the time to reach the platform in Morris water maze, indicating memory impairment in the AlCl3-treated group, but co-administration of naringin showed significant improvement. The Rotarod test demonstrated a decrease in muscle coordination in the AlCl3-treated group, while it was improved in the AlCl3 + N group. Neurochemical analysis of the hippocampus and cerebellum revealed that AlCl3 significantly increased lipid peroxidation and oxidative stress and decreased levels of reduced glutathione. Administration of naringin ameliorated these neurochemical changes via its antioxidant properties. Cerebellar immunohistochemical expression for microtubule assembly (tau protein) and oxidative stress (iNOS) increased in A1C13-treated group. On the other hand, the expression of the autophagic marker (LC3) in the cerebellum showed a marked decline in AlCl3-treated group. Western blot analysis confirmed the cerebellar immunohistochemical findings. Collectively, these findings suggested that naringin could contribute to the combat of oxidative and autophagic stress in the cerebellum of AlCl3-induced AD.

Evaluation of histological and ultrastructural changes provoked by prenatal tramadol on postnatal cortical cerebellar neuronal development in rats: possible implication of Ki67, GFAP and MicroRNA-7/P53 signalling trajectories

“…GCs with extensive vacuolations, an irregular nuclear membrane, a dilated Golgi complex and a marked decrease in granule cell precursors are observed in tramadol-treated groups. The observed morphological alterations in the GCL as a result of tramadol treatment in the present study are consistent with previous research indicating that cerebellar granule neurons are particularly susceptible to oxidative stress-related conditions (Kaur et al 2007 ; Hassan et al 2022 ). Cerebellar granule cell neurons are characterized by their high energy demand and comparatively low ATP levels, in addition to their heightened transcriptional activity of genes linked to oxidative stress and inflammatory responses (Wang et al 2009 ).…”

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

“…A number of flavonoids have also been shown to have neuroprotective and neuroregenerative properties. Preclinical studies in rodent, pig, and monkey models of AD, PD, HD, and ALS [ 34 , 249 , 250 , 251 , 252 , 253 , 254 , 255 ] have also demonstrated that flavonoids have properties that counter neuroinflammation, prevent the neurotoxic effects of pathological protein aggregates of amyloid and hyperphosphorylated tau protein, free radical generation from peroxidation of lipids, and that brain tissues are rich in phospholipids that are susceptible to oxygen radical release during neuroinflammation. Some flavonoids act as monoamine oxidase inhibitors, combat apoptosis, are neuroprotective, promote neurogenesis and memory, and reduce cognitive decline [ 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 ].…”

Phytic acid attenuates acetaminophen-induced hepatotoxicity via modulating iron-mediated oxidative stress and SIRT-1 expression in mice

“…Three different colored images were created using a color deconvolution plug-in and the H-DAB-vector as the selected color: green, brown, and blue. The DAB images (brown in color) were calibrated using area fraction ( Hassan et al, 2022 ). The threshold was adjusted for more precision.…”