细胞生物学
内质网
金丝桃苷
程序性细胞死亡
药理学
生物
兰尼定受体
信号转导
淀粉样前体蛋白
神经毒性
化学
细胞凋亡
阿尔茨海默病
生物化学
内科学
医学
芦丁
毒性
有机化学
抗氧化剂
疾病
作者
Linlin Song,Yuan Qu,Yong Tang,Xi Chen,Hang Hong Lo,Qu Li,Yun Xiao Yun,Vincent Kam Wai Wong,Rui Long Zhang,Hui Miao Wang,Meng Han Liu,Wei Zhang,Hui Xia Zhang,Joyce Tsz Wai Chan,Cai Ren Wang,Jian Wu,Betty Yuen Kwan Law
出处
期刊:Redox biology
[Elsevier BV]
日期:2023-02-14
卷期号:61: 102637-102637
被引量:30
标识
DOI:10.1016/j.redox.2023.102637
摘要
Alzheimer's disease is a neurodegenerative disorder characterized by a decline in cognitive function. The β-amyloid (Aβ) hypothesis suggests that Aβ peptides can spontaneously aggregate into β-fragment-containing oligomers and protofibrils, and this activation of the amyloid pathway alters Ca2+ signaling in neurons, leading to neurotoxicity and thus apoptosis of neuronal cells. In our study, a blood-brain barrier crossing flavonol glycoside hyperoside was identified with anti-Aβ aggregation, BACE inhibitory, and neuroprotective effect in cellular or APP/PSEN1 double transgenic Alzheimer's disease mice model. While our pharmacokinetic data confirmed that intranasal administration of hyperoside resulted in a higher bio-availability in mice brain, further in vivo studies revealed that it improved motor deficit, spatial memory and learning ability of APP/PSEN1 mice with reducing level of Aβ plaques and GFAP in the cortex and hippocampus. Bioinformatics, computational docking and in vitro assay results suggested that hyperoside bind to Aβ and interacted with ryanodine receptors, then regulated cellular apoptosis via endoplasmic reticulum-mitochondrial calcium (Ca2+) signaling pathway. Consistently, it was confirmed that hyperoside increased Bcl2, decreased Bax and cyto-c protein levels, and ameliorated neuronal cell death in both in vitro and in vivo model. By regulating Aβ-induced cell death via regulation on Ca2+ signaling cascade and mitochondrial membrane potential, our study suggested that hyperoside may work as a potential therapeutic agent or preventive remedy for Alzheimer's disease.
科研通智能强力驱动
Strongly Powered by AbleSci AI