Beta-asarone improves cognitive function by suppressing neuronal apoptosis in the beta-amyloid hippocampus injection rats.
Elevated levels of beta-amyloid (Abeta) in the brains being a hallmark of Alzheimer's disease (AD) have been believed to play a critical role in the cognitive dysfunction that occurs in AD. Recent evidence suggests that Abeta induces neuronal apoptosis in the brain and in primary neuronal cultures. In this study, we investigated the effects of beta-asarone, the major ingredient of Acorus Tatarinowii Schott, on cognitive function and neuronal apoptosis in Abeta hippocampus injection rats and its mechanism of action. The results show that the Abeta (1-42) injection caused impairments in spatial reference memory in a Morris water maze task and apoptosis in hippocampus. Oral administration of beta-asarone with three different dose (12.5, 25, or 50 mg/kg) for 28 d ameliorated Abeta (1-42)-induced cognitive impairment and reversed the increase of apoptosis in the hippocampus. Abeta-induced c-Jun N-terminal kinase (JNK) results in phosphorylation, subsequent down-regulation of Bcl-2 and Bcl-w expression, and caspase-3 activation. Beta-asarone attenuate Abeta (1-42)-induced neuronal apoptosis in hippocampus by reversal down-regulation of Bcl-2, Bcl-w, caspase-3 activation, and JNK phosphorylation. These results suggest that beta-asarone may be a potential candidate for development as a therapeutic agent to manage cognitive impairment associated with conditions such as Alzheimer's disease.
Geng
Yutao
Y
The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
Li
Chengchong
C
Liu
Jicheng
J
Xing
Guihua
G
Zhou
Li
L
Dong
Miaoxian
M
Li
Xueyan
X
Niu
Yingcai
Y
D029023:Acorus / Q000737:chemistry*; D000081248:Allylbenzene Derivatives; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000840:Anisoles / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000081248:Allylbenzene Derivatives; D016229:Amyloid beta-Peptides; D000840:Anisoles; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C012195:asarone; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3