Zou De-Jia, Wang Gang, Liu Ji-Cheng, Dong Miao-Xian, Li Xiao-Ming, Zhang Chun, Zhou Li, Wang Rui, Niu Ying-Cai
The Institute of Medicine, Qiqihar Medical University, Qiqihar, China.
Pharmazie. 2011 Jan;66(1):44-51.
Beta-amyloid (Abeta) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that beta-asarone improves cognitive function by suppressing neuronal apoptosis in vivo. In this study, we assessed the neuroprotective effects of beta-asarone against the toxicity of Abeta in relation to the mitochondria-mediated cell death process, and to elucidated the role of the ASK1/MKK7/JNK and mitochondrial pathways in beta-asarone-induced neuroprotection in SH-SY5Y cells. Our results show that beta-asarone afforded protection against Abeta-induced toxicity by inhibiting apoptosis in SH-SY5Y cells. This result was also confirmed by caspase-9 and caspase-3 activity assays. Expression of p-ASK1, p-MKK7, p-JNK, Bax, Bad, and cytochrome c release decreased after pretreatment with beta-asarone in SH-SY5Y cells exposed to A1-42. Interestingly, these effects of beta-asarone against Abeta1-42 insult were enhanced by ASK1 siRNA. These findings suggest that beta-asarone prevents Abeta1-42-induced neurotoxicity through attenuating neuronal apoptosis, and might be a potential preventive or therapeutic agent for AD.
β-淀粉样蛋白（Aβ）毒性被认为是引发阿尔茨海默病（AD）中突触丧失及随后神经元变性的原因。我们之前证明了β-细辛醚通过在体内抑制神经元凋亡来改善认知功能。在本研究中，我们评估了β-细辛醚针对Aβ毒性的神经保护作用，这与线粒体介导的细胞死亡过程相关，并阐明了ASK1/MKK7/JNK和线粒体途径在β-细辛醚诱导的SH-SY5Y细胞神经保护中的作用。我们的结果表明，β-细辛醚通过抑制SH-SY5Y细胞中的凋亡来抵御Aβ诱导的毒性。这一结果也通过caspase-9和caspase-3活性测定得到了证实。在用Aβ1-42处理的SH-SY5Y细胞中，用β-细辛醚预处理后，p-ASK1、p-MKK7、p-JNK、Bax、Bad的表达以及细胞色素c的释放均下降。有趣的是，ASK1小干扰RNA增强了β-细辛醚对Aβ1-42损伤的这些作用。这些发现表明，β-细辛醚通过减轻神经元凋亡来预防Aβ1-42诱导的神经毒性，可能是AD的一种潜在预防或治疗药物。
