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.
PLoS One. 2024 Jul 15;19(7):e0305358. doi: 10.1371/journal.pone.0305358. eCollection 2024.
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.
亨廷顿病（HD）是一种极其有害的常染色体遗传性神经退行性疾病。运动功能障碍、精神障碍和认知缺陷是该病的特征。本研究旨在探讨 6-姜酚对大鼠 3-硝基丙酸（3-NPA）诱导的 HD 是否具有保护作用。
雄性 Wistar 大鼠 30 只，6-姜酚（10 和 20 mg/kg，口服）给药 1 小时后，腹腔注射 3-NPA（10 mg/kg），共 15 天。进行行为测试，包括窄道行走、转棒试验和握力试验。评估促进氧化应激的生化试验[超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）、过氧化氢酶（CAT）和丙二醛（MDA）]，包括神经递质 5-羟色胺（5-HT）、多巴胺（DA）、去甲肾上腺素（NE）、高香草酸（HVA）、（3,4-二羟基苯乙酸（DOPAC）、γ-氨基丁酸（GABA）和 5-羟吲哚乙酸（5-HIAA）的变化，核因子 kappa-B（NF-κB）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、脑源性神经营养因子（BDNF）和核因子红细胞 2 相关因子 2（Nrf2）。使用 AutoDock 工具将 6-姜酚对接至 TNF-α（2AZ5）、NF-κB（1SVC）、BDNF[1B8M]和 Nrf2[5FZN]蛋白的活性部位。
6-姜酚组的行为活动明显优于 3-NPA 注射对照组大鼠。此外，3-NPA 诱导的神经递质、生化和神经炎症指数显著改变，6-姜酚可有效逆转这些改变。6-姜酚对 BDNF 表现出有利的负结合能（-9.271 kcal/mol）。
本研究在实验动物模型中证明了 6-姜酚对 3-NPA 诱导的大鼠 HD 的神经保护作用。免疫组织化学分析和 Western blot 支持所提出的机制，但需要进一步研究以明确确认。
