Hypoestoxide reduces neuroinflammation and α-synuclein accumulation in a mouse model of Parkinson's disease

J Neuroinflammation. 2015 Dec 18;12:236. doi: 10.1186/s12974-015-0455-9.


Background: Deposition of α-synuclein and neuroinflammation are key pathological features of Parkinson's disease (PD). There is no cure for the disease; however, targeting the pathological features might be available to modulate the disease onset and progression. Hypoestoxide (HE) has been demonstrated as a NF-κB modulator, thereby acting as a potential anti-inflammatory and anti-cancer drug.

Methods: In order to assess the effect of HE in a mouse model of PD, mThy1-α-syn transgenic mice received intraperitoneal (IP) injections of either vehicle or HE (5 mg/kg) daily for 4 weeks.

Results: Treatment of HE decreased microgliosis, astrogliosis, and pro-inflammatory cytokine gene expression in α-syn transgenic mice. HE administration also prevented the loss of dopaminergic neurons and ameliorated motor behavioral deficits in the α-syn transgenic mice, and α-synuclein pathology was significantly reduced by treatment of HE. In addition, increased levels of nuclear phosphorylated NF-κB in the frontal cortex of α-syn transgenic mice were significantly reduced by HE administration.

Conclusions: These results support the therapeutic potential of HE for PD and other α-synuclein-related diseases.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Diterpenes / pharmacology
  • Diterpenes / therapeutic use*
  • Female
  • Humans
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / metabolism
  • Mice
  • Mice, Transgenic
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Neocortex / drug effects
  • Neocortex / metabolism
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • alpha-Synuclein / antagonists & inhibitors*
  • alpha-Synuclein / biosynthesis*


  • Diterpenes
  • NF-kappa B
  • alpha-Synuclein
  • hypoestoxide