茉莉酸甲酯通过抑制氧化应激、释放促炎细胞因子以及下调 NF-κB 和 α-突触核蛋白表达的免疫阳性细胞，消除鱼藤酮诱导的帕金森样症状。
Methyl jasmonate abrogates rotenone-induced parkinsonian-like symptoms through inhibition of oxidative stress, release of pro-inflammatory cytokines, and down-regulation of immnopositive cells of NF-κB and α-synuclein expressions in mice.
机构信息
Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Ago-Iwoye, Nigeria; Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
出版信息
Neurotoxicology. 2019 Sep;74:172-183. doi: 10.1016/j.neuro.2019.07.003. Epub 2019 Jul 20.
Oxidative stress and neuroinflammation play key roles in the initiation and progression of Parkinson's disease (PD), a neurodegenerative disorder, associated with the loss of nigrostriatal dopaminergic pathway. Thus, compounds that can mitigate oxidative stress and neuroinflammation are being investigated as promising agents for the treatment of PD. This study was designed to evaluate the effects of methyl jasmonate (MJ), a potent antioxidant and anti-inflammatory compound on parkinsonian-like symptoms and the underlying biochemical changes induced by rotenone (Rot) in mice. To this end, the effects of graded doses of MJ (25, 50 and100 mg/kg, i.p.) on motor dysfunctions, cognitive and depressive-like disorders induced by Rot (2.5 mg/kg, i.p.) were evaluated. The specific brain regions (striatum, prefrontal cortex and hippocampus) of the animals were processed for various biochemical studies. Rot-treated mice showed reduced motor activity, postural instability, cognitive and depressive-like disorders. Rot also increased brain levels of malondialdehyde (MDA), nitrite, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and acetyl-cholinesterase (AChE) activity. Moreover, Rot reduced the concentration of glutathione (GSH) and increased immnopositive cells of NF-κB and α-synuclein expressions in these brain regions. However, pretreatment with MJ, attenuated the parkinsonian-like symptoms and reduced the brain levels of MDA/nitrite, TNF-α and IL-6 induced by Rot. MJ also reduced AChE activity and down-regulate the expressions of NF-κB and α-synuclein in the brain of Rot-treated mice. These findings suggest that MJ has anti-parkinsonian-like activity, which may be related to the inhibition of oxidative stress, release of pro-inflammatory cytokines, and down regulation of NF-κB and α-synuclein expressions.
氧化应激和神经炎症在帕金森病（PD）的发生和进展中起关键作用，PD 是一种神经退行性疾病，与黑质纹状体多巴胺能通路的丧失有关。因此，能够减轻氧化应激和神经炎症的化合物被作为治疗 PD 的有希望的药物进行研究。本研究旨在评估茉莉酸甲酯（MJ）对鱼藤酮（Rot）诱导的帕金森样症状和潜在生化变化的影响。为此，评估了不同剂量的 MJ（25、50 和 100mg/kg，ip）对 Rot（2.5mg/kg，ip）诱导的运动功能障碍、认知和抑郁样障碍的影响。对动物的特定脑区（纹状体、前额叶皮层和海马体）进行了各种生化研究。Rot 处理的小鼠表现出运动活动减少、姿势不稳定、认知和抑郁样障碍。Rot 还增加了脑内丙二醛（MDA）、亚硝酸盐、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和乙酰胆碱酯酶（AChE）活性。此外，Rot 降低了谷胱甘肽（GSH）的浓度，并增加了这些脑区中 NF-κB 和α-突触核蛋白的免疫阳性细胞表达。然而，MJ 预处理可减轻帕金森样症状，并降低 Rot 诱导的脑内 MDA/亚硝酸盐、TNF-α和 IL-6 水平。MJ 还降低了 AChE 活性，并下调了 Rot 处理的小鼠脑中 NF-κB 和α-突触核蛋白的表达。这些发现表明 MJ 具有抗帕金森样活性，这可能与抑制氧化应激、释放促炎细胞因子以及下调 NF-κB 和α-突触核蛋白表达有关。
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