beta-Asarone Inhibits Neuronal Apoptosis via the CaMKII/CREB/Bcl-2 Signaling Pathway in an in vitro Model and A beta PP/PS1 Mice

作者：Wei Gang; Chen Yun bo; Chen Dong Feng^*; Lai Xiao Ping; Liu Dong Hui; Deng Ru Dong; Zhou Jian Hong; Zhang Sai Xia; Li Yi Wei; Lii Hui; Liu Liu Fang; Wang Qi; Nie Hui

来源：Journal of Alzheimer's Disease, 2013, 33(3): 863-880.

DOI：10.3233/JAD-2012-120865

• Alzheimer's disease
• beta-asarone
• Bcl-2
• CaMKII
• neuronal apoptosis
• phospho-CREB-binding protein

beta-Asarone, an active component of the Acori graminei rhizome that has been used as traditional Chinese herb, has been reported to be capable of inhibiting neuronal apoptosis. However, the signaling mechanism underlying the inhibitory effect of beta-asarone has remained elusive. This study was aimed to investigate whether the CaMKII signaling pathway is involved in the beta-asaronemediated neuroprotection. Using PC12 cells and primary cultures of cortical neurons treated with amyloid-beta (A beta)(1-40) or A beta(1-42) peptide, we demonstrated that beta-asarone can protect PC12 cells and cortical neurons and inhibit neuronal apoptosis by activating the CaMKII-alpha/p-CREB/Bcl-2 pathway. Moreover, CaMKII-alpha overexpression enhanced the beta-asarone-induced p-CREB-Bcl-2 expression and anti-apoptotic effects. Interestingly, suppression of CaMKII-alpha by siRNA or a specific inhibitor can significantly reduce the beta-asarone-induced p-CREB and Bcl-2 expression and A beta(1-40) induced neuronal apoptosis in PC12 cells. A beta PP/PS1 mice at the age of 3 months and age-matched wild-type mice were intragastrically administered beta-asarone (7 mg/kg/day, 21 mg/kg/day) or a vehicle daily for 4 months. beta-asarone improved cognitive function of the A beta PP/PS1 mice and reduced neuronal apoptosis in the cortex of the A beta PP/PS1 mice. A significant increase in CaMKII/CREB/Bcl-2 expression was observed in the cortex of the A beta PP/PS1 mice treated with beta-asarone. In summary, our observations demonstrated that beta-asarone can inhibit neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in in vitro models and in A beta PP/PS1 mice. Therefore, beta-asarone can be used as a potential therapeutic agent in the long-term treatment of Alzheimer's disease.

• 单位
  广州中医药大学