Anusha Chandran, Sumathi Thangarajan, Joseph Leena Dennis
Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamil Nadu, India.
Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamil Nadu, India.
Chem Biol Interact. 2017 May 1;269:67-79. doi: 10.1016/j.cbi.2017.03.016. Epub 2017 Apr 4.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra which is associated with oxidative stress, neuroinflammation and apoptosis. Apigenin (AGN), a non-mutagenic flavone found in fruits and vegetables, exhibits a variety of biological effects including anti-apoptotic, anti-inflammatory, and free radical scavenging activities. The current study was aimed to investigate the neuroprotective effects and molecular mechanisms of AGN in a rat model of PD induced by rotenone (ROT). Unilateral stereotaxic intranigral infusion of ROT caused the loss of tyrosine hydroxylase (TH) immunoreactivity in striatum and substantia nigra. AGN treatment (10 and 20 mg/kg, i.p.) showed a significant improvement in behavioral, biochemical and mitochondrial enzyme activities as compared to ROT exposed rats. The mRNA expression of inflammatory markers and neurotrophic factors was quantified by reverse transcriptase polymerase chain reaction (RT-PCR). Administration of AGN significantly attenuated the upregulation of NF-κB gene expression in ROT induced group and prevented the neuroinflammation in substantia nigra pars compacta (SNpc). Further, AGN inhibited the release of pro-inflammatory cytokines TNF- α, IL-6 and pro-inflammatory enzyme iNOS-1 induced by ROT. Additionally, AGN prevents the reduction of neurotrophic factors BDNF and GDNF mRNA expression in ROT lesioned rats. Immunoblot results illustrated that AGN treatment downregulated α-synuclein aggregation and upregulated the TH protein expression as well as dopamine D2 receptor (D2R) expression in ROT lesioned rats. Thus, the present findings collectively suggest that AGN exerts its neuroprotection in ROT model of PD and may act as an effective agent for treatment of PD.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质中多巴胺能神经元的丧失，这与氧化应激、神经炎症和细胞凋亡有关。芹菜素（AGN）是一种存在于水果和蔬菜中的非致突变黄酮，具有多种生物学效应，包括抗凋亡、抗炎和自由基清除活性。本研究旨在探讨AGN对鱼藤酮（ROT）诱导的PD大鼠模型的神经保护作用及其分子机制。单侧立体定向黑质内注射ROT导致纹状体和黑质中酪氨酸羟化酶（TH）免疫反应性丧失。与暴露于ROT的大鼠相比，AGN治疗（10和20mg/kg，腹腔注射）在行为、生化和线粒体酶活性方面有显著改善。通过逆转录聚合酶链反应（RT-PCR）对炎症标志物和神经营养因子的mRNA表达进行定量。AGN给药显著减弱了ROT诱导组中NF-κB基因表达的上调，并预防了黑质致密部（SNpc）的神经炎症。此外，AGN抑制了ROT诱导的促炎细胞因子TNF-α、IL-6和促炎酶iNOS-1的释放。此外，AGN可防止ROT损伤大鼠中神经营养因子BDNF和GDNF mRNA表达的降低。免疫印迹结果表明，AGN治疗可下调ROT损伤大鼠中α-突触核蛋白的聚集，并上调TH蛋白表达以及多巴胺D2受体（D2R）表达。因此，本研究结果共同表明，AGN在ROT诱导的PD模型中发挥神经保护作用，可能是治疗PD的有效药物。
