金丝桃苷
磷酸化
蛋白激酶B
高磷酸化
化学
细胞生物学
神经毒性
药理学
贯叶连翘
癌症研究
生物化学
生物
毒性
有机化学
作者
Wanyue Huang,Ping Cheng,Kaiyuan Yu,Yaling Han,Miao Song,Yanfei Li
标识
DOI:10.1016/j.biopha.2017.09.114
摘要
Aluminum (Al) is a neurotoxicant and cause β-amyloid (Aβ) peptides aggregation and tau hyperphosphorylation. Hyperforin (HF) is one of the major active constituents of the extracts of St. John's Wort (Hypericum perforatum), can treat Alzheimer's disease (AD) and other diseases involving peptide accumulation and cognition impairment. To determine the effects of HF on Al-induced Aβ formation and tau hyperphosphorylation, PC12 cells were cultured and treated with Al-malt (500μM) and/or HF (1μM). The results showed that HF treatment significantly attenuated Al-malt-induced Aβ1-42 production by reducing the expressions of APP, BACE1 and PS1, while increasing the expressions of sAPPα, ADAM9/10/17, and tau phosphorylation in PC12 cells. In addition, HF treatment also increased phosphorylation of AKT (Ser473) and inhibited GSK-3β activity by increasing phosphorylation of GSK-3β (Ser9). These results indicated that HF may exert the protection via regulating the AKT/GSK-3β signaling to reduce Aβ production and tau phosphorylation in PC12 cells. Furthermore, these results could lead a possible therapeutics for the management of Al neurotoxicity.
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