α-Asarone Ameliorates Memory Deficit in Lipopolysaccharide-Treated Mice via Suppression of Pro-Inflammatory Cytokines and Microglial Activation

Abstract

α-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of α-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of α-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. α-Asarone significantly reduced TNF-α and IL-1β mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of α-asarone treatment. α-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. α-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of α-asarone treatment. In the Morris water maze test, α-asarone significantly prolonged the swimming time spent in the target and peri-target zones. α-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by α-asarone may be one of the mechanisms for the α-asarone-mediated ameliorating effect on memory deficits.

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

“…Apart from its traditional claims, scientific reports showed that AGR can be used as neuroprotective (Jiang et al, 2012;Limon et al, 2009;Manikandan and Devi, , anticonvulsant (Pages et al, 2010) and hyperlipidemic agent (Garduno et al, 1997). Recent evidence showed that a-asarone ameliorated memory deficits in LPS-treated mice via its antiinflammatory actions (Shin et al, 2014). However, the effects of the active constituent α-asarone isolated from AGR in PDrelated neuroinflammatory conditions and the intrinsic mechanisms involved in regulating microglia-mediated signaling pathways were not documented.…”

IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

“…Antibody specificity for IL-1β was confirmed by preabsorption with recombinant mouse IL-1β, which blocked further staining with the IL-1β antibody. This antibody has been previously used for immunohistochemistry in mouse 38,39 and detects both the inactive, precursor and active form of IL-1β 40 . The Iba-1 antibody 41,42 and NeuN antibody 43,44 have been extensively used in mice.…”

Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy

“…Compelling evidence demonstrates that compounds such as alpha-tocopherol, edaravone, alpha-asarone having antioxidant properties can reduce neuroinflammation and neuronal degeneration in various models of epilepsy (Betti et al, 2011;Miyamoto et al, 2008;Shin et al, 2014). Curcumin (diferuloyl methane) is a polyphenolic diketone found in Curcuma longa Linn.…”