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

• Published in: The Journal of nutritional biochemistry Vol. 25; no. 7; pp. 801 - 806
• Main Authors: Leem, Eunju, Nam, Jin Han, Jeon, Min-Tae, Shin, Won-Ho, Won, So-Yoon, Park, Sang-Joon, Choi, Myung-Sook, Jin, Byung Kwan, Jung, Un Ju, Kim, Sang Ryong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2014
• Subjects: 1-Methyl-4-phenylpyridinium; 1-Methyl-4-phenylpyridinium - toxicity; Animals; Citrus; Disease Models, Animal; Dopamine - physiology; Female; Flavanones - pharmacology; GDNF; Glial Cell Line-Derived Neurotrophic Factor - biosynthesis; Glial Cell Line-Derived Neurotrophic Factor - immunology; Naringin; Neuroprotection; Neuroprotective Agents - pharmacology; Parkinson Disease - physiopathology; Parkinson's disease; Rats, Sprague-Dawley; Substantia Nigra - drug effects; 1-Methyl-4-phenylpyridinium; Neuroprotection; Naringin; Parkinson's disease; GDNF
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2014.03.006

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.