title: Beta-asarone attenuates neuronal apoptosis induced by Beta amyloid in rat hippocampus.
abstract: Neurodegenerative disorders, such as Alzheimer's disease (AD), is associated with the loss of neuronal cells, and it has been suggested that apoptosis is a crucial pathway in neuronal loss in AD patients. Recent evidence suggests that amyloid beta peptide (Abeta) induces neuronal apoptosis in the brain and in primary neuronal cultures. In this study, we investigated the impact of beta-asarone against the apoptosis induced by Abeta in rat hippocampus. The results showed that intrahippocampal injections of Abeta (1-42) caused apoptosis in rat hippocampus. Oral administration of beta-asarone (12.5, 25, or 50 mg/kg) for 28 d reverse the increase in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells in the hippocampus tissue. Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in AD. Therefore, we investigated nuclear translocation of apoptosis induction factors. Our results showed that beta-asarone afforded a beneficial inhibition on both mRNA and protein expression of Bad, Bax, and cleavage of caspases 9 in rat hippocampus following intrahippocampal injections of Abeta (1-42). Our further investigation revealed that ASK1, p-MKK7, and p-c-Jun were significantly decreased after beta-asarone treatment, implicating that the modulation of ASK1/c-JNK-mediated intracellular signaling cascades might be involved in therapeutic effect of beta-asarone against Abeta toxicity. Taken together, these results suggest that beta-asarone may be a potential candidate for development as a therapeutic agent for AD.
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Liu
authors.forename: Chengchong
authors.initials: C
authors.lastname: Li
authors.forename: Guihua
authors.initials: G
authors.lastname: Xing
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Miaoxian
authors.initials: M
authors.lastname: Dong
authors.forename: Yutao
authors.initials: Y
authors.lastname: Geng
authors.forename: Xueyan
authors.initials: X
authors.lastname: Li
authors.forename: Jiaming
authors.initials: J
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Dejia
authors.initials: D
authors.lastname: Zou
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Niu
mesh_terms: D000284:Administration, Oral; D000081248:Allylbenzene Derivatives; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053453:Caspase 9 / Q000378:metabolism; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D015195:Drug Design; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D048848:MAP Kinase Kinase Kinase 5 / Q000502:physiology; D008297:Male; D009474:Neurons / Q000473:pathology*; D010446:Peptide Fragments / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D000081248:Allylbenzene Derivatives; D016229:Amyloid beta-Peptides; D000840:Anisoles; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C012195:asarone; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D048031:JNK Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D004253:DNA Nucleotidylexotransferase; D053453:Caspase 9