title: 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.
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Shin
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Cheong
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Yong-Mo
authors.initials: YM
authors.lastname: Koo
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Sooyong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Chung-Ku
authors.initials: CK
authors.lastname: Noh
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Son
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Chulhun
authors.initials: C
authors.lastname: Kang
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea.
authors.forename: Nak-Won
authors.initials: NW
authors.lastname: Sohn
keywords: IL-1β; Memory deficit; Microglial activation; Neuroinflammation; TNF-α; α-Asarone