Albiflorin ameliorates memory deficits in APP/PS1 transgenic mice via ameliorating mitochondrial dysfunction
Albiflorin ameliorates memory deficits in APP/PS1 transgenic mice via ameliorating mitochondrial dysfunction
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DOI：
10.1016/j.brainres.2019.05.037
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发表时间：
2019-09
期刊：
影响因子：
2.9
通讯作者：
Yi-Jun Xu;Yu Mei;Xue-Qing Shi;Yifan Zhang;Xinyue Wang;L. Guan;Qi Wang;Huafeng Pan
中科院分区：
文献类型：
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作者：
Yi-Jun Xu;Yu Mei;Xue-Qing Shi;Yifan Zhang;Xinyue Wang;L. Guan;Qi Wang;Huafeng Pan
白芍苷是中药白芍的主要成分，对β-淀粉样蛋白（Aβ）诱导的阿尔茨海默病细胞损伤有明显的改善作用，但其作用机制尚不清楚。我们使用7个月大的APP/PS1小鼠来确定albiflorin是否能够预防阿尔茨海默病。我们发现，4周的albiflorin（20 mg/kg/d和40 mg/kg/d）灌胃给药改善了APP/PS1小鼠的记忆缺陷。Albiflorin通过降低APP/PS1小鼠脑中的Aβ水平和增加PSD-95、突触素和突触素1水平来赋予突触保护作用。芍药苷通过降低活性氧（ROS）水平和提高Mn-SOD活性发挥抗氧化作用。Albiflorin还降低了APP/PS1小鼠中Drp 1的水平，增加了Mfn 1，Mfn 2和Opa 1的水平，并改善了线粒体形态。通过增加海马和皮质中Bcl-2和Bcl-xl的水平，降低Bax、caspase-3和细胞色素酶的水平，以及通过减少APP/PS1小鼠前顶叶皮质中的凋亡细胞数量，Albiflorin抑制凋亡的线粒体途径。总之，在APP/PS1小鼠中，albiflorin治疗改善了线粒体功能，减少了脑中的Aβ沉积，并改善了记忆缺陷。这些结果表明，albiflorin可能作为一个潜在的抗痴呆药物。
Albiflorin, the main component of Radix Paeoniae Alba, has been shown to ameliorate injury in cell models of Alzheimer’s disease induced by amyloid-β (Aβ), but the mechanism is unclear. We used 7-month-old APP/PS1 mice to determine whether albiflorin is capable of protecting against Alzheimer’s disease. We found that four weeks of intragastric administration of albiflorin (20 mg/kg/d and 40 mg/kg/d) ameliorated memory deficits in APP/PS1 mice. Albiflorin conferred synaptic protection by decreasing Aβ levels and increasing PSD-95, synaptophysin and synapsin 1 levels in the brains of APP/PS1 mice. Albiflorin played an antioxidative role by reducing reactive oxygen species (ROS) levels and elevating Mn-SOD activity in the brain. Albiflorin also reduced the level of Drp1, increased the levels of Mfn1, Mfn2 and Opa1 and improved mitochondrial morphology in APP/PS1 mice. Albiflorin inhibited the mitochondrial pathway of apoptosis by increasing the levels of Bcl-2 and Bcl-xl and decreasing the levels of Bax, caspase-3 and cytochromecin both the hippocampus and the cortex and by reducing the number of apoptotic cells in the anterior parietal cortex of the APP/PS1 mice. In conclusion, treatment with albiflorin improved mitochondrial function, reduced Aβ deposition in the brain and ameliorated memory deficits in APP/PS1 mice. These findings indicate that albiflorin may serve as a potential antidementia drug.