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

• Published in: PloS one Vol. 19; no. 7; p. e0305358
• Main Authors: Jambi, Ebtihaj J, Alamri, Abdulaziz, Afzal, Muhammad, Al-Abbasi, Fahad A, Al-Qahtani, Salwa D, Almalki, Naif A R, Bawadood, Azizah Salim, Alzarea, Sami I, Sayyed, Nadeem, Kazmi, Imran
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.07.2024; Public Library of Science (PLoS)
• Subjects: 3-Nitropropionic acid; Acetic acid; Animal cognition; Animals; Antioxidants; Behavior; Behavior, Animal - drug effects; Biochemical tests; Biology and Life Sciences; Brain research; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Catalase; Catechols - chemistry; Catechols - pharmacology; Cell death; Cytokines - metabolism; Deoxyribonucleic acid; Dihydroxyphenylacetic acid; Disease; DNA; Dopamine; Drug dosages; Enzymes; Free radicals; Glutathione; Grip strength; Homovanillic acid; Huntington Disease - chemically induced; Huntington Disease - drug therapy; Huntington Disease - metabolism; Huntington's disease; Huntingtons disease; Indoleacetic acid; Male; Medicine and Health Sciences; Mental disorders; Molecular docking; Molecular Docking Simulation; Motor ability; Neurodegenerative diseases; Neuroprotection; Neuroprotective Agents - pharmacology; Neurotransmitters; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Nitro Compounds; Norepinephrine; Oxidative stress; Oxidative Stress - drug effects; Physical Sciences; Propionates - pharmacology; Rats; Rats, Wistar; Research and Analysis Methods; Serotonin; Shogaols; Signal Transduction - drug effects; Superoxide dismutase; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Western blotting; γ-Aminobutyric acid; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0305358

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. 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. 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. 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.