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J Nutr Biochem. 2014 Jul;25(7):801-6. doi: 10.1016/j.jnutbio.2014.03.006. Epub 2014 Apr 1.

Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease.

Author information

1
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.
2
Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
3
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea; Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 305-600, Korea.
4
Department of Biochemistry and Signaling Disorder Research Center, Chungbuk National University, Cheongju 361-763, Korea.
5
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.
6
Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 702-701, Korea.
7
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; Institute of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701, Korea; Brain Science and Engineering Institute, Kyungpook National University, Daegu 700-842, Korea. Electronic address: srk75@knu.ac.kr.

Abstract

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.

KEYWORDS:

1-Methyl-4-phenylpyridinium; GDNF; Naringin; Neuroprotection; Parkinson's disease

PMID:
24797334
DOI:
10.1016/j.jnutbio.2014.03.006
[Indexed for MEDLINE]

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