Neuroprotective effects of puerarin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson's disease model in mice

Phytother Res. 2014 Feb;28(2):179-86. doi: 10.1002/ptr.4975. Epub 2013 Mar 20.

Abstract

Puerarin, an active component of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep is well-known for its anti-oxidative and neuroprotective activities. Although anti-Parkinson's disease activity of puerarin was reported in both of in vivo and in vitro model, detailed mechanisms are not clarified. In this study, we addressed that puerarin attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits, dopaminergic neuronal degeneration and dopamine depletion. Puerarin administration enhanced glutathione (GSH) activity, glial cell line-derived neurotrophic factor (GDNF) expression and PI3K/Akt pathway activation, which might ameliorate MPTP injection-induced progressive elevation of reactive oxygen species (ROS) formation in mice. In addition to the effect on ROS, puerarin ameliorated MPTP-reduced lysosome-associated membrane protein type 2A (Lamp 2A) expression. Taken together, our data demonstrate that puerarin attenuates MPTP-induced dopaminergic neuronal degeneration via modulating GDNF expression, PI3K/Akt pathway and GSH activation, which subsequently ameliorate MPTP-induced ROS formation and decrease of Lamp 2A expression.

Keywords: Lamp 2A; Parkinson's disease; glial cell line-derived neurotrophic factor; puerarin; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects
  • Animals
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Glutathione / metabolism
  • Isoflavones / pharmacology*
  • Lysosomal-Associated Membrane Protein 2 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Degeneration / chemically induced*
  • Neuroprotective Agents / pharmacology*
  • Parkinson Disease / drug therapy*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • Glial Cell Line-Derived Neurotrophic Factor
  • Isoflavones
  • Lysosomal-Associated Membrane Protein 2
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Glutathione
  • Dopamine
  • puerarin