alpha-Asarone Ameliorates Memory Deficit in Lipopolysaccharide-Treated Mice via Suppression of Pro-Inflammatory Cytokines and Microglial Activation.
- Author:
Jung Won SHIN
1
;
Young Jin CHEONG
;
Yong Mo KOO
;
Sooyong KIM
;
Chung Ku NOH
;
Young Ha SON
;
Chulhun KANG
;
Nak Won SOHN
Author Information
1. Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Republic of Korea. sohnnw@khu.ac.kr
- Publication Type:Original Article
- Keywords:
alpha-Asarone;
Memory deficit;
Microglial activation;
TNF-alpha;
IL-1beta;
Neuroinflammation
- MeSH:
Animals;
Cell Size;
Cytokines*;
Head;
Hippocampus;
Immunohistochemistry;
Learning;
Maze Learning;
Memory;
Memory Disorders*;
Mice*;
Microglia;
Neurons;
RNA, Messenger;
Swimming;
Tumor Necrosis Factor-alpha;
Up-Regulation
- From:Biomolecules & Therapeutics
2014;22(1):17-26
- CountryRepublic of Korea
- Language:English
-
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-1beta 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.
