title: A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Mao
authors.affiliation: 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.
authors.forename: Shichao
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Feng
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Yi Eve
authors.initials: YE
authors.lastname: Sun
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: 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.|School of Life Science and Technology, and the Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, 200092, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
mesh_terms: D029023:Acorus / Q000737:chemistry*; D000367:Age Factors; D000081248:Allylbenzene Derivatives; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D004365:Drugs, Chinese Herbal; C012195:asarone; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK cascade; asarone; neural progenitor cell proliferation; neurodegeneration; traditional herb medicines