Puerarin attenuates neuronal degeneration in the substantia nigra of 6-OHDA-lesioned rats through regulating BDNF expression and activating the Nrf2/ARE signaling pathway

Brain Res. 2013 Jul 26:1523:1-9. doi: 10.1016/j.brainres.2013.05.046. Epub 2013 Jun 5.

Abstract

An increasing number of studies suggest that oxidative stress is associated with the Parkinsonian process. This study evaluated the potential neuroprotective role of puerarin (PR) on lesioned substantia nigra (SN) induced by 6-hydroxydopamine (6-OHDA). Data from a rotational test showed that PR treatment significantly decreased apomorphine-induced rotations. Both the dopamine (DA) content in the SN and the endogenous expression of brain-derived neurotrophic factor (BDNF) were also elevated by the treatment. Pathological examination showed that dopaminergic neuronal degeneration in the SN was attenuated by PR treatment. Meanwhile, the contents of γ-glutamylcysteine synthetase (γ-GCS), glutathione (GSH) and catalase (CAT) in SN tissue were gradually elevated. Additionally, cytochrome c oxidase (COX) mRNA expression in the SN was markedly up-regulated. At the same time, nuclear factor E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keapl) levels were progressively increased by the PR treatment. Our findings indicated that puerarin effectively protects against 6-OHDA-mediated oxidative stress injury in SN neurons, in which the underlying mechanisms are involved in modulating BDNF expression and activating the Nrf2/ARE signaling pathway.

Keywords: BDNF; Nrf2/ARE signaling pathway; Oxidative stress; Parkinson's disease; Puerarin; Substantia nigra.

MeSH terms

  • Animals
  • Antioxidants* / adverse effects
  • Antioxidants* / pharmacology
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor* / biosynthesis
  • Catalase / metabolism
  • Dopamine / metabolism
  • Electron Transport Complex IV / metabolism
  • Glutamate-Cysteine Ligase / metabolism
  • Glutathione / metabolism
  • Hydroxydopamines
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / biosynthesis
  • Intracellular Signaling Peptides and Proteins / genetics
  • Isoflavones* / adverse effects
  • Isoflavones* / pharmacology
  • Kelch-Like ECH-Associated Protein 1
  • Male
  • NF-E2-Related Factor 2* / biosynthesis
  • Nerve Degeneration* / prevention & control
  • Neuroprotective Agents*
  • Rats
  • Rats, Wistar
  • Signal Transduction* / drug effects
  • Signal Transduction* / physiology
  • Substantia Nigra* / cytology
  • Substantia Nigra* / drug effects
  • Substantia Nigra* / physiology
  • Sympatholytics

Substances

  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Catalase
  • Dopamine
  • Electron Transport Complex IV
  • Glutamate-Cysteine Ligase
  • Glutathione
  • Hydroxydopamines
  • Intracellular Signaling Peptides and Proteins
  • Isoflavones
  • KEAP1 protein, rat
  • Kelch-Like ECH-Associated Protein 1
  • Neuroprotective Agents
  • puerarin
  • Sympatholytics
  • NF-E2-Related Factor 2