DL-3-n-butylphthalide imparts neuroprotection via Nrf2/SIRT3 pathway in a mouse model of vascular dementia.

ABSTRACT

The goal of this study was to explore the mechanism of action of DL-3-n-butylphthalidein (NBP) the treatment of vascular dementia (VD) in mice. A vascular dementia mouse model was established with repeated cerebral ischemia/reperfusion (I/R), followed by administration of two different doses of NBP for 28 days. A Morris water maze was used to detect any changes in spatial cognition, while H&E staining was used to observe any histopathological changes in the hippocampus. The number of Caspase-3 and Caspase-9 positive neurons in the hippocampal CA1 region were also assessed using immunohistochemistry. The expression of Nrf2, Sirt3, and autophagy-related factors LC3 II/I and p62 in the hippocampus were detected by Western blotting. The results indicated that NBP treatment ameliorated learning and memory deficits, attenuated pathological damage in the CA1 regions, and reduced autophagy and apoptosis via the Nrf2/SIRT3 pathway after repeated cerebral I/R. Therefore, NBP treatment can improve the learning and cognitive memory of VD mice, possibly through the inhibition of autophagy and apoptosis mediated by the Nrf2/SIRT3 signaling pathway.