title: Osthole decreases beta amyloid levels through up-regulation of miR-107 in Alzheimer's disease.
abstract: Accumulation of β-amyloid peptide (Aβ) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). Although osthole has been shown to neuroprotective activity in AD, the exact molecular mechanism of its neuroprotective effects has not yet been fully elucidated. Recently, microRNAs (miRNAs) have been reported to regulate multiple aspects of AD development and progression, indicating that targeting miRNAs could be a novel strategy to treat AD. In the current study, we investigated whether a natural coumarin derivative osthole could up-regulate miR-107, resulting in facilitating the cells survival, reducing LDH leakage, inhibiting apoptosis and reducing beta amyloid (Aβ) production in AD. We found that osthole treatment significantly up-regulate miR-107 expression and inhibited BACE1, one of the targets of miR-107. Administration of osthole to APP/PS1 transgenic mice resulted in a significant improvement in learning and memory function, which was associated with a significant a decrease in Aβ in the hippocampal and cortex region of the brain. Our findings demonstrated that osthole plays a neuroprotective activity role in part through up-regulate miR-107 in AD.
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Kong
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Shaoheng
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China. Electronic address: jxyang0520@126.com.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000818:Animals; D000831:Animals, Newborn; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D003374:Coumarins; C555365:MIRN107 microRNA, mouse; D035683:MicroRNAs; D018696:Neuroprotective Agents; C046627:osthol
keywords: Alzheimer’s disease; Aβ; BACE1; Osthole; miRNA-107