L-3-n-butylphthalide Rescues Hippocampal Synaptic Failure and Attenuates Neuropathology in Aged APP/PS1 Mouse Model of Alzheimer's Disease.

Our previous studies showed that L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), improved cognitive ability in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease (AD). It is well known that cognitive deficit of AD is caused by synaptic dysfunction. In this study, we investigated the effect of L-NBP on hippocampal synaptic function in APP/PS1 AD transgenic mice and related mechanisms. Eighteen-month-old APP/PS1 transgenic (Tg) mice were administrated 15 mg/kg L-NBP by oral gavage for 3 months. Synaptic morphology and the thickness of postsynaptic density (PSD) in hippocampal neurons were investigated by electron microscope. The dendritic spines, Aβ plaques, and glial activation were detected by staining. The expressions of synapse-related proteins were observed by Western blotting. L-NBP treatment significantly increased the number of synapses and apical dendritic thorns and the thickness of PSD, increased the expression levels of synapse-associated proteins including PSD95, synaptophysin (SYN), β-catenin, and GSK-3β, and attenuated Aβ plaques and neuroinflammatory responses in aged APP/PS1 Tg mice. L-NBP may restore synaptic and spine function in aged APP Tg mice through inhibiting Aβ plaques deposition and neuroinflammatory response. Wnt/β-catenin signaling pathway may be involved in L-NBP-related restoration of synaptic function.

Zhang Y ，Huang LJ ，Shi S ，Xu SF ，Wang XL ，Peng Y ... -  《-》

L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AβPP/PS1-Alzheimer's transgenic mice.

Peng Y ，Hu Y ，Xu S ，Li P ，Li J ，Lu L ，Yang H ，Feng N ，Wang L ，Wang X ... -  《-》

L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer's disease.

Peng Y ，Sun J ，Hon S ，Nylander AN ，Xia W ，Feng Y ，Wang X ，Lemere CA ... -  《-》

L-3-n-Butylphthalide improves synaptic and dendritic spine plasticity and ameliorates neurite pathology in Alzheimer's disease mouse model and cultured hippocampal neurons.

Huang L ，Lan J ，Tang J ，Kang Y ，Feng X ，Wu L ，Peng Y ... -  《-》

L-3-n-Butylphthalide Regulates Proliferation, Migration, and Differentiation of Neural Stem Cell In Vitro and Promotes Neurogenesis in APP/PS1 Mouse Model by Regulating BDNF/TrkB/CREB/Akt Pathway.

Lei H ，Zhang Y ，Huang L ，Xu S ，Li J ，Yang L ，Wang L ，Xing C ，Wang X ，Peng Y ... -  《-》