The citrus flavonoid "Nobiletin" impedes STZ-induced Alzheimer's disease in a mouse model through regulating autophagy mastered by SIRT1/FoxO3a mechanism.
Autor: | El-Maraghy SA; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt., Reda A; Expanded Programme of Immunization (EPI), Ministry of Health, Cairo, Egypt., Essam RM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.; Biology Department, School of Pharmacy, Newgiza University, Giza, Egypt., Kortam MA; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. mona.kortam@pharma.cu.edu.eg. |
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Jazyk: | angličtina |
Zdroj: | Inflammopharmacology [Inflammopharmacology] 2023 Oct; Vol. 31 (5), pp. 2701-2717. Date of Electronic Publication: 2023 Aug 19. |
DOI: | 10.1007/s10787-023-01292-z |
Abstrakt: | The prominence of autophagy in the modulation of neurodegenerative disorders has sparked interest to investigate its stimulation in Alzheimer's disease (AD). Nobiletin possesses several bioactivities such as anti-inflammation, antioxidation, and neuroprotection. Consequently, the study's aim was to inspect the possible neurotherapeutic impact of Nobiletin in damping AD through autophagy regulation. Mice were randomly assigned into: Group I which received DMSO, Groups II, III, and IV obtained STZ (3 mg/kg) intracerebroventricularly once with Nobiletin (50 mg/kg/day; i.p.) in Group III and Nobiletin with EX-527 (2 mg/kg, i.p.) in Group IV. Interestingly, Nobiletin ameliorated STZ-induced AD through enhancing the motor performance and repressing memory defects. Moreover, Nobiletin de-escalated hippocampal acetylcholinesterase (AChE) activity and enhanced acetylcholine level while halting BACE1 and amyloid-β levels. Meanwhile, Nobiletin stimulated the autophagy process through activating the SIRT1/FoxO3a, LC3B-II, and ATG7 pathway. Additionally, Nobiletin inhibited Akt pathway and controlled the level of NF-κB and TNF-α. Nobiletin amended the oxidative stress through enhancing GSH and cutting down MDA levels. However, EX527, SIRT1 inhibitor, counteracted the neurotherapeutic effects of Nobiletin. Therefore, the present study provides a strong verification for the therapeutic influence of Nobiletin in AD. This outcome may be assigned to autophagy stimulation through SIRT1/FoxO3a, inhibiting AChE activity, reducing neuroinflammation and oxidative stress. (© 2023. The Author(s).) |
Databáze: | MEDLINE |
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