Albiflorin ameliorates memory deficits in APP/PS1 transgenic mice via ameliorating mitochondrial dysfunction

Abstract

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 cytochrome c in 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.