Research & Development of New Drugs, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
J Alzheimers Dis. 2013;33(3):863-80. doi: 10.3233/JAD-2012-120865.
β-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 β-asarone has remained elusive. This study was aimed to investigate whether the CaMKII signaling pathway is involved in the β-asarone mediated neuroprotection. Using PC12 cells and primary cultures of cortical neurons treated with amyloid-β (Aβ)(1-40) or Aβ(1-42) peptide, we demonstrated that β-asarone can protect PC12 cells and cortical neurons and inhibit neuronal apoptosis by activating the CaMKII-α/p-CREB/Bcl-2 pathway. Moreover, CaMKII-α overexpression enhanced the β-asarone-induced p-CREB-Bcl-2 expression and anti-apoptotic effects. Interestingly, suppression of CaMKII-α by siRNA or a specific inhibitor can significantly reduce the β-asarone-induced p-CREB and Bcl-2 expression and Aβ(1-40) induced neuronal apoptosis in PC12 cells. AβPP/PS1 mice at the age of 3 months and age-matched wild-type mice were intragastrically administered β-asarone (7 mg/kg/day, 21 mg/kg/day) or a vehicle daily for 4 months. β-asarone improved cognitive function of the AβPP/PS1 mice and reduced neuronal apoptosis in the cortex of the AβPP/PS1 mice. A significant increase in CaMKII/CREB/Bcl-2 expression was observed in the cortex of the AβPP/PS1 mice treated with β-asarone. In summary, our observations demonstrated that β-asarone can inhibit neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in in vitro models and in AβPP/PS1 mice. Therefore, β-asarone can be used as a potential therapeutic agent in the long-term treatment of Alzheimer's disease.
β-细辛脑，一种菖蒲根茎中的活性成分，已被用作传统中药，据报道能抑制神经元凋亡。然而，β-细辛脑抑制作用的信号机制仍不清楚。本研究旨在探讨 CaMKII 信号通路是否参与β-细辛脑介导的神经保护作用。我们使用 PC12 细胞和皮质神经元原代培养物，用淀粉样β肽（Aβ）（1-40）或 Aβ（1-42）处理，证明β-细辛脑可通过激活 CaMKII-α/p-CREB/Bcl-2 通路来保护 PC12 细胞和皮质神经元，抑制神经元凋亡。此外，CaMKII-α过表达增强了β-细辛脑诱导的 p-CREB-Bcl-2 表达和抗凋亡作用。有趣的是，用 siRNA 或特异性抑制剂抑制 CaMKII-α可显著减少β-细辛脑诱导的 p-CREB 和 Bcl-2 表达以及 Aβ（1-40）诱导的 PC12 细胞凋亡。3 月龄 AβPP/PS1 小鼠和同龄野生型小鼠每日给予β-细辛脑（7mg/kg/天，21mg/kg/天）或载体灌胃 4 个月。β-细辛脑改善了 AβPP/PS1 小鼠的认知功能，并减少了 AβPP/PS1 小鼠皮质中的神经元凋亡。在β-细辛脑处理的 AβPP/PS1 小鼠皮质中观察到 CaMKII/CREB/Bcl-2 表达显著增加。总之，我们的观察结果表明，β-细辛脑可以通过体外模型和 AβPP/PS1 小鼠中的 CaMKII/CREB/Bcl-2 信号通路抑制神经元凋亡。因此，β-细辛脑可作为治疗阿尔茨海默病的潜在治疗剂长期使用。
