Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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α-Asarone Ameliorates Memory Deficit in Lipopolysaccharide-Treated Mice via Suppression of Pro-Inflammatory Cytokines and Microglial Activation

  • Shin, Jung-Won (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Cheong, Young-Jin (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Koo, Yong-Mo (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kim, Sooyong (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Noh, Chung-Ku (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Son, Young-Ha (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kang, Chulhun (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Sohn, Nak-Won (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
  • Received : 2013.11.26
  • Accepted : 2014.01.10
  • Published : 2014.01.31
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Abstract

${\alpha}$-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of ${\alpha}$-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 ${\alpha}$-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. ${\alpha}$-Asarone significantly reduced TNF-${\alpha}$ and IL-$1{\beta}$ 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 ${\alpha}$-asarone treatment. ${\alpha}$-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. ${\alpha}$-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 ${\alpha}$-asarone treatment. In the Morris water maze test, ${\alpha}$-asarone significantly prolonged the swimming time spent in the target and peri-target zones. ${\alpha}$-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 ${\alpha}$-asarone may be one of the mechanisms for the ${\alpha}$-asarone-mediated ameliorating effect on memory deficits.

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References

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