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

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. alpha-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 alpha-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 alpha-asarone in vivo. The results indicated that alpha-asarone significantly attenuated the LPS-stimulated increase in neuroinflammatory responses and suppressed pro-inflammatory cytokine production in BV-2 cells. Mechanistic study revealed that alpha-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 alpha-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 alpha-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. (C) 2015 Elsevier Ltd. All rights reserved.