Mao Jianxin, Huang Shichao, Liu Shangfeng, Feng Xiao-Lin, Yu Miao, Liu Junjun, Sun Yi Eve, Chen Guoliang, Yu Yang, Zhao Jian, Pei Gang
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China.
Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China.
Aging Cell. 2015 Oct;14(5):784-96. doi: 10.1111/acel.12356. Epub 2015 May 25.
Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and β-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders.
异常的神经祖细胞(NPC)增殖和自我更新与年龄相关的神经退行性变以及包括阿尔茨海默病(AD)在内的神经退行性疾病有关。石菖蒲是一种用于对抗认知衰退的传统中草药。在本研究中,我们发现石菖蒲提取物(AT)及其活性成分细辛醚可促进NPC增殖。口服AT可增强成年和老年小鼠以及转基因AD模型小鼠海马中的NPC增殖和神经发生。AT及其组分还增强了体外培养的NPC的增殖。进一步分析确定α-细辛醚和β-细辛醚是AT促进神经发生的两种活性成分。我们的机制研究表明,AT和细辛醚激活了细胞外信号调节激酶(ERK),但未激活Akt,这是神经发生的两个关键激酶级联反应。一致地,抑制ERK活性有效地阻断了AT或细辛醚对NPC增殖的增强作用。我们的研究结果表明,可口服的AT和细辛醚可作为预防性和再生性治疗剂,以促进神经发生,对抗年龄相关的神经退行性变和神经退行性疾病。