المؤلفون: Chengchong LI, Dejia ZOU, Gang WANG, Guihua XING, Jiaming LI, Jicheng LIU, Li ZHOU, Miaoxian DONG, Xueyan LI, Yingcai NIU, Yutao GENG

المصدر: YAKUGAKU ZASSHI. 2010, 130(5):737

المؤلفون: Yingcai Niu, Li Zhou, Xueyan Li, Gang Wang, Chengchong Li, Jicheng Liu, Dejia Zou, Guihua Xing, Miaoxian Dong, Yutao Geng, Jiaming Li

المصدر: YAKUGAKU ZASSHI. 130:737-746

مصطلحات موضوعية: Male, Amyloid beta, Administration, Oral, Pharmaceutical Science, Allylbenzene Derivatives, Apoptosis, Anisoles, Pharmacology, MAP Kinase Kinase Kinase 5, Hippocampus, Rats, Sprague-Dawley, Alzheimer Disease, DNA Nucleotidylexotransferase, medicine, Animals, ASK1, Caspase, bcl-2-Associated X Protein, Neurons, Amyloid beta-Peptides, biology, c-jun, JNK Mitogen-Activated Protein Kinases, P3 peptide, medicine.disease, Caspase 9, Peptide Fragments, Rats, Terminal deoxynucleotidyl transferase, Drug Design, Immunology, biology.protein, bcl-Associated Death Protein, Alzheimer's disease, Signal Transduction

الوصف: 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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a86a355b417aa3a1e5203eb9b59f44b6Test
https://doi.org/10.1248/yakushi.130.737Test