State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
J Neurosci. 2013 Aug 7;33(32):13138-49. doi: 10.1523/JNEUROSCI.4790-12.2013.
Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.
阿尔茨海默病（AD）主要表现为一种进行性的大脑神经退行性疾病，最终导致不可逆转的智力丧失。β-淀粉样蛋白（Aβ）诱导的神经退行性变被认为是 AD 的主要病理机制，抑制 Aβ 产生或促进其清除是抗 AD 研究的有前途的治疗策略之一。在这里，我们报告说，来自牛蒡（Arctium lappa（L.）的天然产物牛蒡子苷既能通过抑制β-位淀粉样前体蛋白裂解酶 1 的表达来抑制 Aβ 的产生，又能通过抑制 AKT/mTOR 信号通路和激活 AMPK/Raptor 通路来增强自噬，从而促进 Aβ 的清除，这在细胞和 APP/PS1 转基因 AD 模型小鼠中得到了研究。此外，结果表明，牛蒡子苷在小鼠中的治疗能显著降低 Aβ 的形成和老年斑，并有效改善 AD 小鼠的记忆障碍，这强烈凸显了牛蒡子苷在抗 AD 药物发现中的潜力。
