A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.
A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.
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一种治疗阿尔茨海默病的草药及其活性成分促进神经祖细胞增殖
作者：
Mao J;Huang S;Liu S;Feng XL;Yu M;Liu J;Sun YE;Chen G;Yu Y;Zhao J;Pei G
异常的神经祖细胞（NPC）增殖和自我更新与年龄相关的神经变性和神经退行性疾病（包括阿尔茨海默病（AD））有关。石菖蒲是一种对抗认知能力下降的传统中草药。在这项研究中，我们发现菖蒲提取物（AT）及其活性成分细辛酮可促进鼻咽癌增殖。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-细辛脑和β-细辛脑是AT促进神经发生的两种活性成分。我们的机制研究表明，AT 和细辛酮激活细胞外信号调节激酶 (ERK)，但不激活 Akt，这是神经发生的两个关键激酶级联。一致地，抑制 ERK 活性可有效阻止 AT 或细辛醚对 NPC 增殖的增强作用。我们的研究结果表明，AT 和细辛酮可以口服，可以作为预防和再生治疗剂，促进神经发生，对抗年龄相关的神经退行性疾病和神经退行性疾病。
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.