Dl-3-n-butylphthalide, a natural antioxidant, protects dopamine neurons in rotenone models for Parkinson's disease

Neurobiol Aging. 2012 Aug;33(8):1777-91. doi: 10.1016/j.neurobiolaging.2011.03.007. Epub 2011 Apr 23.


In the absence of a cure for Parkinson's disease, development of preventive medications for this devastating disease is particularly encouraged. Dl-3-n-butylphthalide (NBP), an established natural antioxidant for clinical stroke treatment in China, can reportedly reduce beta-amyloid-induced neuronal toxicity in cultured neuronal cells, and attenuate neurodegenerative changes in aged rats. However, whether or not NBP confers neuroprotection in parkinsonian models is still unknown. In this study, we investigated the effects of NBP in rotenone models for Parkinson's diseases. In a cellular model, pretreatment with NBP enhanced cell viability by decreasing nuclear fragmentation, retaining mitochondrial membrane potential, and preventing reactive oxygen species (ROS) from generation. In a rodent model, 2-week treatment with NBP was able to ameliorate apomorphine-evoked rotations by 48% and rescue dopaminergic (DA) neurons by 30% and striatal DA terminal by 49%. Furthermore, NBP upregulated the vesicular monoamine transporter 2 gene expression in vitro and in vivo. Together, NBP protects DA neurons likely by reducing oxidative stress, offering an alternative neuroprotective medication for Parkinson's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antiparkinson Agents / administration & dosage*
  • Benzofurans / administration & dosage*
  • Cell Line
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / pathology*
  • Humans
  • Neuroprotective Agents / administration & dosage
  • Parkinsonian Disorders / chemically induced*
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / prevention & control*
  • Rats
  • Rotenone*
  • Treatment Outcome


  • Antioxidants
  • Antiparkinson Agents
  • Benzofurans
  • Neuroprotective Agents
  • Rotenone
  • 3-n-butylphthalide