Nobiletin protects dopaminergic neurons in the 1-methyl-4-phenylpyridinium-treated rat model of Parkinson's disease

J Med Food. 2015 Apr;18(4):409-14. doi: 10.1089/jmf.2014.3241. Epub 2014 Oct 17.

Abstract

This study investigated the effect of nobiletin, a flavonoid found in citrus fruits, on the degeneration of dopaminergic (DA) neurons in a neurotoxin model of Parkinson's disease (PD). 1-Methyl-4-phenylpyridinium (MPP(+)) was unilaterally injected into the median forebrain bundle of rat brains (to generate a neurotoxin model of PD) with or without daily intraperitoneal injection of nobiletin. Our results showed that nobiletin treatment at 10 mg/kg bw, but not at 1 or 20 mg/kg bw, significantly protected DA neurons in the substantia nigra (SN) of MPP(+)-treated rats. In parallel to the neuroprotection, nobiletin treatment at 10 mg/kg inhibited microglial activation and preserved the expression of the glial cell line-derived neurotrophic factor, which is a therapeutic agent against PD, in the SN. These results suggest that the proper supplementation with nobiletin may protect against the neurodegeneration involved in PD.

Keywords: GDNF; MPP+; dopaminergic neuron; microglia; neuroprotection; nobiletin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Animals
  • Disease Models, Animal
  • Dopaminergic Neurons / cytology
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Female
  • Flavones / administration & dosage*
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Humans
  • Neuroprotective Agents / administration & dosage*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra

Substances

  • Flavones
  • Glial Cell Line-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • nobiletin
  • 1-Methyl-4-phenylpyridinium