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在阿尔茨海默病大鼠模型中,α-蒎烯的神经保护作用是通过抑制TNF-α/NF-κB信号通路介导的。

Neuroprotective effect of alpha-pinene is mediated by suppression of the TNF-α/NF-κB pathway in Alzheimer's disease rat model.

作者信息

Khan-Mohammadi-Khorrami Mohammad-Kazem, Asle-Rousta Masoumeh, Rahnema Mehdi, Amini Rahim

机构信息

Department of Physiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran.

Department of Biology, Zanjan Branch, Islamic Azad University, Zanjan, Iran.

出版信息

J Biochem Mol Toxicol. 2022 May;36(5):e23006. doi: 10.1002/jbt.23006. Epub 2022 Feb 17.

DOI:10.1002/jbt.23006
PMID:35174932
Abstract

Monoterpene alpha-pinene possesses antioxidant, cardioprotective, and neuroprotective properties. We evaluated the effect of alpha-pinene on oxidative/nitrosative stress, neuroinflammation, and molecular and behavioral changes induced by beta-amyloid (Aβ) in rats and investigated the possible mechanisms of these outcomes. Male Wistar rats received alpha-pinene (50 mg/kg intraperitoneally) for 14 consecutive days after intrahippocampal injection of Aβ . Alpha-pinene decreased malondialdehyde and nitric oxide levels, increased glutathione content, and enhanced catalase activity in Aβ-injected rats. Also, messenger RNA expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, nuclear factor κB, and N-methyl- d-aspartate receptor subunits 2A and 2B reduced in the hippocampus of these animals. Besides this, alpha-pinene repressed the Aβ -induced reduction of nicotinic acetylcholine receptor α7 subunit and brain-derived neurotrophic factor expression. Treatment with alpha-pinene caused Aβ-receiving rats to spend more time in the target quadrant in the Morris water maze test and led to an increase in percentages of open arm entrance and time spent in the open arm in the elevated plus-maze test. We concluded that alpha-pinene strengthens the antioxidant system and prevents neuroinflammation in the hippocampus of rats receiving Aβ. It improves spatial learning and memory and reduces anxiety-like behavior in these animals. Consequently, alpha-pinene alleviates Aβ-induced oxidative/nitrosative stress, neuroinflammation, and behavioral deficits. It is probably a suitable candidate for the treatment of neurodegenerative diseases.

摘要

单萜α-蒎烯具有抗氧化、心脏保护和神经保护特性。我们评估了α-蒎烯对大鼠由β-淀粉样蛋白(Aβ)诱导的氧化/亚硝化应激、神经炎症以及分子和行为变化的影响,并研究了这些结果的可能机制。雄性Wistar大鼠在海马内注射Aβ后连续14天腹腔注射α-蒎烯(50mg/kg)。α-蒎烯降低了注射Aβ大鼠的丙二醛和一氧化氮水平,增加了谷胱甘肽含量,并增强了过氧化氢酶活性。此外,这些动物海马中肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、核因子κB以及N-甲基-D-天冬氨酸受体亚基2A和2B的信使核糖核酸表达降低。除此之外,α-蒎烯抑制了Aβ诱导的烟碱型乙酰胆碱受体α7亚基和脑源性神经营养因子表达的降低。在莫里斯水迷宫试验中,用α-蒎烯治疗使接受Aβ的大鼠在目标象限花费更多时间,并且在高架十字迷宫试验中使进入开放臂的百分比和在开放臂中花费的时间增加。我们得出结论,α-蒎烯增强了接受Aβ大鼠海马中的抗氧化系统并预防神经炎症。它改善了这些动物的空间学习和记忆,并减少了焦虑样行为。因此,α-蒎烯减轻了Aβ诱导的氧化/亚硝化应激、神经炎症和行为缺陷。它可能是治疗神经退行性疾病的合适候选药物。

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