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Abstract Aim Alzheimer's disease (AD), a neurodegenerative disease, was characterized by the loss of memory and progressive cognitive deterioration. Up to now, there has no effective drugs to cure or delay the state of illness. Increasing evidence indicates that hyperphosphorylated tau protein plays a pivotal role in the occurrence and development of AD. Therefore, in present study, we aim to investigate whether osthole (OST) could decrease hyperphosphorylated tau protein in AD and the underlying mechanism. Main methods The ability of learning and memory was detected by Morris Water Maze. The pathological changes were detected by H&E staining. The percentage of cells apoptosis was detected by TUNEL assay in vivo and Flow Cytometry in intro. The expressions of tau protein and related proteins in PI3K/Akt/GSK-3β signaling pathway were detected by Western Blot. Key findings We found that OST could significantly improve learning and memory dysfunction, ameliorate the histology structure of damaged neural cells in hippocampal area. Moreover, we also found that OST could decrease tau protein phosphorylation as well as inhibit cells apoptosis. To explore the underlying mechanism, we used LY294002 to block PI3K/Akt/GSK-3β signaling pathway, the results from Western bolt showed that the expression of related proteins in PI3K signaling pathway were decreased with LY294002 treated. Significance Taken together, the results indicated that OST could decrease phosphorylated tau levels via activation of PI3K/Akt/GSK-3β signaling pathway. Thus, this study demonstrated that OST might be a potential candidate for the treatment of AD. [ABSTRACT FROM AUTHOR]

Abstract Aim Alzheimer's disease (AD) is a slowly progressing neurodegenerative disorder that attributed to the increase of amyloid precursor protein (APP). Recently, evidence indicates that microRNA alterations are involved in the development of AD. In this paper, we demonstrated whether osthole could delay the occurrence of AD by regulating miRNA. Methods Microarray was used to discover differential miRNAs in AD. The target genes regulated by miRNA were predicted by databases; The protective effects of osthole on APP/PS1 mice were determined by Morris Water Maze, H&E and Nissl staining; The APP-SH-SY5Y cells were transfected with miRNA-101a-3p inhibitor, the expression of miRNA-101a-3p and APP mRNA in APP/PS1 mice and APP-SH-SY5Y cells were detected by RT-PCR; And western blot and ICC staining were used to detect the APP and Aβ proteins expression. Key findings MiRNA-101a-3p was the osthole-mediated miRNA in AD and APP is the target gene. Osthole could increase the learning and memory ability in APP/PS1 mice and inhibit APP mRNA/protein expression by up-regulating miRNA-101a-3p. For exploring the underlying mechanism, miR-101a-3p inhibitor was transfected into the APP-SH-SY5Y cells. We can know that osthole had a protective effect on APP-SH-SY5Y cells, and it could raise miRNA-101a-3p expression and inhibit APP mRNA/protein expression, the formation of Aβ protein was inhibited too. Significance These results emphasized that osthole had a protective effect on APP/PS1 mice and APP-SH-SY5Y cells. The main cause was due to osthole could inhibit APP expression by up-regulating miRNA-101a-3p so as to help delay the occurrence of AD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of osthole on the expression of amyloid precursor protein (APP) in Alzheimer's disease (AD) cell model and its mechanism., Methods: The SH-SY5Y cell with over expression of APP was established by transfection by liposome 2000. The cells were treated with different concentrations of osthole, and the cell viability was determined by MTT and lactate dehydrogenase (LDH) assay. The differentially expressed miRNAs with and without osthole treatment were detected by miRNA array, and the target genes binding to the differentially expressed miRNAs were identified and verified by databases and Cytoscape. After the inhibitor of the differentially expressed miRNA was transduced into cells, the changes of APP and amyloid β (Aβ) protein were determined by immunofluorescence cytochemistry, and the mRNA expression of APP was determined by RT-PCR., Results: The AD cell model with over expression of APP was established successfully. The results of MTT and LDH assay showed that osthole had a protective effect on cells and alleviated cell damage. miR-101a-3p was identified as the differentially expressed miRNA, which was binding to the 3'-UTR of APP. Compared with APP group, the expression of APP and Aβ protein and APP mRNA increased in the miR-101a-3p inhibitor group (all P <0.01), while the expression of APP and Aβ protein and APP mRNA decreased in the cells with osthole treatment (all P <0.01)., Conclusions: Osthole inhibits the expression of APP by up-regulating miR-101a-3p in AD cell model.