2010 年 130 巻 5 号 p. 737-746
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 (Aβ) induces neuronal apoptosis in the brain and in primary neuronal cultures. In this study, we investigated the impact of β-asarone against the apoptosis induced by Aβ in rat hippocampus. The results showed that intrahippocampal injections of Aβ (1-42) caused apoptosis in rat hippocampus. Oral administration of β-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 β-amyloid (Aβ)-induced neuronal toxicity in AD. Therefore, we investigated nuclear translocation of apoptosis induction factors. Our results showed that β-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 Aβ (1-42). Our further investigation revealed that ASK1, p-MKK7, and p-c-Jun were significantly decreased after β-asarone treatment, implicating that the modulation of ASK1/c-JNK-mediated intracellular signaling cascades might be involved in therapeutic effect of β-asarone against Aβ toxicity. Taken together, these results suggest that β-asarone may be a potential candidate for development as a therapeutic agent for AD.
