α-Asarone attenuates microglia-mediated neuroinflammation by inhibiting NF kappa B activation and mitigates MPTP-induced behavioral deficits in a mouse model of Parkinson's disease

Neuropharmacology. 2015 Oct;97:46-57. doi: 10.1016/j.neuropharm.2015.04.037. Epub 2015 May 15.

Abstract

The selective loss of dopaminergic neurons in Parkinson's disease (PD) is associated with microglial activation. Therefore, the importance of early therapeutic intervention to inhibit microglial activation would be an effective strategy to alleviate the progression of PD. α-Asarone, an active compound found in Araceae and Annonaceae plant species has been used to improve various disease conditions including central nervous system disorders. In the present study the in vitro and in vivo therapeutic effects of α-asarone isolated from the rhizome of Acorus gramineus Solander was evaluated on microglia-mediated neuroinflammation and neuroprotection. Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells were used to evaluate in vitro effects. 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mouse model of PD was developed to study the neuroprotective effects of α-asarone in vivo. The results indicated that α-asarone significantly attenuated the LPS-stimulated increase in neuroinflammatory responses and suppressed pro-inflammatory cytokine production in BV-2 cells. Mechanistic study revealed that α-asarone inhibited the LPS-stimulated activation via regulation of nuclear factor kappa-B by blocking degradation of inhibitor kappa B-alpha signaling in BV-2 microglial cells. In in vivo studies, MPTP intoxication to mice resulted in brain microglial activation and significant behavioral deficits. Prophylactic treatment with α-asarone suppressed microglial activation and attenuated PD-like behavioral impairments as assessed by the Y-maze and pole tests. Taken together, these data demonstrate that α-asarone is a promising neuroprotective agent that should be further evaluated and developed for future prevention and treatment of microglia-mediated neuroinflammatory conditions including PD.

Keywords: MPTP; Microglia; Neuroinflammation; Parkinson's disease; α-Asarone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anisoles / chemistry
  • Anisoles / isolation & purification
  • Anisoles / pharmacology*
  • Brain / drug effects
  • Brain / immunology
  • Brain / pathology
  • Cell Line
  • Cytokines / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology
  • Dopaminergic Neurons / physiology
  • Dose-Response Relationship, Drug
  • Lipopolysaccharides
  • MPTP Poisoning / drug therapy*
  • MPTP Poisoning / immunology
  • MPTP Poisoning / pathology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Microglia / immunology
  • Microglia / pathology
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • NF-kappa B / metabolism*
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / physiology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*

Substances

  • Anisoles
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Neuroprotective Agents
  • asarone