丹参
脑啡肽酶
药理学
神经保护
免疫印迹
淀粉样前体蛋白
化学
内质网
β淀粉样蛋白
未折叠蛋白反应
胰岛素降解酶
酶
医学
中医药
生物化学
阿尔茨海默病
内科学
疾病
基因
肽
替代医学
病理
作者
Xiaoqi Liu,Haijun Tian,Guangliang Wu,Liang Qiao,Ye-Feng Cai,Qi Wang,Shijie Zhang
标识
DOI:10.1016/j.ijbiomac.2023.127923
摘要
In Alzheimer's disease (AD), amyloid-beta (Aβ) plays a crucial role in pathogenesis. Clearing Aβ from the brain is considered as a key therapeutic strategy. Previous studies indicated that Salvia miltiorrhiza (Danshen) could protect against AD. However, the main anti-AD components in Danshen and their specific mechanisms are not clear. In this study, pharmacological network analysis indicated that Tanshinone IIA (Tan IIA) was identified as the key active compound in Danshen contributing to protect against AD. Then, APP/PS1 double transgenic mice were employed to examine the neuroprotective effect of Tan IIA. APP/PS1 mice (age, 6 months) were administered (10 and 20 mg/kg) for 8 weeks. Tan IIA improved learning and anxiety behaviors in APP/PS1 mice. Furthermore, Tan IIA reduced oxidative stress, inhibited neuronal apoptosis, improved cholinergic nervous system and decreased endoplasmic reticulum stress in the brain of APP/PS1 mice. Moreover, Tan IIA treatment reduced the level of Aβ. Molecular docking result showed that Tan IIA might block AD by upregulating Aβ-degrading enzymes. Western blot results confirmed that the expressions of insulin degrading enzymes (IDE) and neprilysin (NEP) were significantly increased after Tan IIA treatment, which demonstrated that Tan IIA improved AD by increasing Aβ-degrading enzymes.
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