School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea; KNU Creative BioResearch Group (BK21 Plus Program), Kyungpook National University, Daegu 702-701, Korea.
Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
J Nutr Biochem. 2014 Jul;25(7):801-6. doi: 10.1016/j.jnutbio.2014.03.006. Epub 2014 Apr 1.
This study investigated the effect of naringin, a major flavonoid in grapefruit and citrus fruits, on the degeneration of the nigrostriatal dopaminergic (DA) projection in a neurotoxin model of Parkinson's disease (PD) in vivo and the potential underlying mechanisms focusing on the induction of glia-derived neurotrophic factor (GDNF), well known as an important neurotrophic factor involved in the survival of adult DA neurons. 1-Methyl-4-phenylpyridinium (MPP(+)) was unilaterally injected into the medial forebrain bundle of rat brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. To ascertain whether naringin-induced GDNF contributes to neuroprotection, we further investigated the effects of intranigral injection of neutralizing antibodies against GDNF in the MPP(+) rat model of PD. Our observations demonstrate that naringin could increase the level of GDNF in DA neurons, contributing to neuroprotection in the MPP(+) rat model of PD, with activation of mammalian target of rapamycin complex 1. Moreover, naringin could attenuate the level of tumor necrosis factor-α in microglia increased by MPP(+)-induced neurotoxicity in the substantia nigra. These results indicate that naringin could impart to DA neurons the important ability to produce GDNF as a therapeutic agent against PD with anti-inflammatory effects, suggesting that naringin is a beneficial natural product for the prevention of DA degeneration in the adult brain.
这项研究调查了柚皮苷（葡萄柚和柑橘类水果中的主要类黄酮）对帕金森病（PD）神经毒素模型中黑质纹状体多巴胺能（DA）投射退化的影响，以及潜在的机制，重点关注胶质细胞衍生的神经营养因子（GDNF）的诱导，GDNF 是一种已知的参与成年 DA 神经元存活的重要神经营养因子。1-甲基-4-苯基吡啶（MPP(+)）通过每日腹腔注射，单侧注射到大鼠大脑的中脑前束，建立 PD 的神经毒素模型，同时存在或不存在柚皮苷。为了确定柚皮苷诱导的 GDNF 是否有助于神经保护，我们进一步研究了在 MPP(+) PD 大鼠模型中，向黑质内注射 GDNF 中和抗体的影响。我们的观察结果表明，柚皮苷可以增加 DA 神经元中的 GDNF 水平，有助于 MPP(+)诱导的 PD 大鼠模型中的神经保护，这与雷帕霉素靶蛋白复合物 1 的激活有关。此外，柚皮苷可以减轻 MPP(+)诱导的神经毒性引起的黑质中小胶质细胞中肿瘤坏死因子-α的水平。这些结果表明，柚皮苷可以赋予 DA 神经元产生 GDNF 的重要能力，作为治疗 PD 的一种治疗剂，具有抗炎作用，表明柚皮苷是预防成年大脑中 DA 退化的有益天然产物。
