A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.
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.
['Mao|Jianxin|J|', 'Huang|Shichao|S|', 'Liu|Shangfeng|S|', 'Feng|Xiao-Lin|XL|', 'Yu|Miao|M|', 'Liu|Junjun|J|', 'Sun|Yi Eve|YE|', 'Chen|Guoliang|G|', 'Yu|Yang|Y|', 'Zhao|Jian|J|', 'Pei|Gang|G|']
D029023:Acorus D000367:Age Factors D000081248:Allylbenzene Derivatives D000544:Alzheimer Disease D000818:Animals D000840:Anisoles D049109:Cell Proliferation D002478:Cells, Cultured D004195:Disease Models, Animal D004365:Drugs, Chinese Herbal D048049:Extracellular Signal-Regulated MAP Kinases D051379:Mice D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D058953:Neural Stem Cells D055495:Neurogenesis
neurodegeneration asarone ERK cascade neural progenitor cell proliferation traditional herb medicines