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

Autor: Hassan HM; Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Elnagar MR; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.; Department of Pharmacology, College of Pharmacy, The Islamic University, Najaf, Iraq., Abdelrazik E; Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Mahdi MR; Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Hamza E; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Horus University, Damietta, Egypt., Elattar EM; Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt., ElNashar EM; Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia.; Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Banha, Egypt., Alghamdi MA; Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia.; Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha, Saudi Arabia., Al-Qahtani Z; Neurology Section, Department of Internal Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia., Al-Khater KM; Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., Aldahhan RA; Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., ELdesoqui M; Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.; Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: Frontiers in neuroanatomy [Front Neuroanat] 2022 Oct 14; Vol. 16, pp. 1012422. Date of Electronic Publication: 2022 Oct 14 (Print Publication: 2022).
DOI: 10.3389/fnana.2022.1012422
Abstrakt: 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 (AlCl 3 )-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) AlCl 3 -recived AlCl 3 (100 mg/kg/d) p.o and (iv) AlCl 3 + Naringin (AlCl 3 + N ) received both AlCl 3 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 AlCl 3 -treated group, but co-administration of naringin showed significant improvement. The Rotarod test demonstrated a decrease in muscle coordination in the AlCl 3 -treated group, while it was improved in the AlCl 3 + N group. Neurochemical analysis of the hippocampus and cerebellum revealed that AlCl 3 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 A1C1 3 -treated group. On the other hand, the expression of the autophagic marker (LC3) in the cerebellum showed a marked decline in AlCl 3 -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 AlCl 3 -induced AD.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AE-k declared a shared affiliation with the authors EMEN, MA, and ZA-Q to the handling editor at the time of review.
(Copyright © 2022 Hassan, Elnagar, Abdelrazik, Mahdi, Hamza, Elattar, ElNashar, Alghamdi, Al-Qahtani, Al-Khater, Aldahhan and ELdesoqui.)
Databáze: MEDLINE