6-shogaol against 3-Nitropropionic acid-induced Huntington's disease in rodents: Based on molecular docking/targeting pro-inflammatory cytokines/NF-κB-BDNF-Nrf2 pathway.

Autor: Jambi EJ; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Alamri A; Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia., Afzal M; Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia., Al-Abbasi FA; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Al-Qahtani SD; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah, Saudi Arabia., Almalki NAR; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Bawadood AS; Basic Medical Sciences Department, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia., Alzarea SI; Department of Pharmacology, College of Pharmacy, Jouf University, Aljouf, Sakaka, Saudi Arabia., Sayyed N; School of Pharmacy, Glocal University, Saharanpur, India., Kazmi I; Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jul 15; Vol. 19 (7), pp. e0305358. Date of Electronic Publication: 2024 Jul 15 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0305358
Abstrakt: Background: Huntington's disease (HD) is an extremely harmful autosomal inherited neurodegenerative disease. Motor dysfunction, mental disorder, and cognitive deficits are the characteristic features of this disease. The current study examined whether 6-shogaol has a protective effect against 3-Nitropropionic Acid (3-NPA)-induced HD in rats.
Methods: A total of thirty male Wistar rats received 6-shogaol (10 and 20 mg/kg, per oral) an hour before injection of 3-NPA (10 mg/kg i.p.) for 15 days. Behavioral tests were performed, including narrow beam walk, rotarod test, and grip strength test. Biochemical tests promoting oxidative stress were evaluated [superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA)], including changes to neurotransmitters serotonin (5-HT), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), (3,4-dihydroxyphenylacetic acid (DOPAC), γ-aminobutyric acid (GABA), and 5-hydroxy indole acetic acid (5-HIAA), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukins-1β (IL-1β), IL-6, brain-derived neurotrophic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2). The 6-shogaol was docked to the active site of TNF-α (2AZ5), NF-κB (1SVC), BDNF) [1B8M], and Nrf2 [5FZN] proteins using AutoDock tools.
Results: The 6-shogaol group significantly improved behavioral activity over the 3-NPA-injected control rats. Moreover, 3-NPA-induced significantly altered neurotransmitters, biochemical and neuroinflammatory indices, which could efficiently be reversed by 6-shogaol. The 6-shogaol showed favorable negative binding energies at -9.271 (BDNF) kcal/mol.
Conclusions: The present investigation demonstrated the neuroprotective effects of 6-shogaol in an experimental animal paradigm against 3-NPA-induced HD in rats. The suggested mechanism is supported by immunohistochemical analysis and western blots, although more research is necessary for definite confirmation.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Jambi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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