L-3-n-butylphthalide improves cognitive impairment of APP/PS1 mice by BDNF/TrkB/PI3K/AKT pathway.

Abstract

L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia and amyloid-beta (Abeta)-induced animal models by inhibiting oxidative injury, neuronal apoptosis and glial activation, regulating amyloid-beta protein precursor (AbetaPP) processing and reducing Abeta generation. The objective of this study was to investigate the effects of L-3-n-butylphthalide on memory impairment and the expression of brain neurotrophic derived factor (BNDF), kinaseB (TrkB), phosphatidylinositol 3 kinase (PI3K) and Akt in APP/PS1 double transgenic mouse models. APP/PS1 double transgenic mice were administered 30 mg/kg•d L-NBP and 10 mg/kg•d L-NBP for one month. The learning and memory ability were studied using the water maze test. Protein expression and transcript levels of genes in the mice hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. The results demonstrated that both 30 mg/kg•d L-NBP and 10 mg/kg•d L-NBP doses of L-NBP significantly increased memory capability and the expression of hippocampal BDNF/TrkB/PI3K/AKT in mice The results suggested that L-NBP treatment may reverse memory impairment in APP/PS1 transgenic mice, and BDNF/TrkB/PI3K/AKT, may be involved in this process.