L-butyl phthalein improves neural function of vascular dementia mice by regulating the PI3K/AKT signaling pathway

Objective: L-3-n-butylphthalide (L-NBP) is a type of anti-ischemic cranial nerve protective drug that may act on vascular dementia (VD). Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt/PKB) signaling pathway can up-regulate B-cell lymphoma 2 (Bcl-2) expression, reduce Reactive Oxygen Species (ROS) production, and alleviate cell Apoptosis. This study aimed at investigating the role of L-NBP on neurological function and cell Apoptosis in VD mouse through regulating PI3K/Akt signaling pathway.

Materials and methods: The mice were divided into four groups, including Sham, VD, VD + solvent, and VD + L-NBP. HT22 cells were cultured in vitro and treated by ischemia/reperfusion (I/R). HT22 cells were divided into four groups, including I/R, VD + solvent, VD + L-NBP, and VD + L-NBP + LY294002 groups. Phosphorylated Akt (p-AKT) and Bcl-2 expressions were tested. ROS content in hippocampus tissue was detected by flow cytometry. Cell Apoptosis was evaluated by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay.

Results: ROS content and cell Apoptosis increased, while p-AKT and Bcl-2 expressions reduced in hippocampus tissue from VD group compared with sham group. L-NBP significantly up-regulated p-AKT and Bcl-2 expressions and decreased ROS content and cell Apoptosis in hippocampus tissue. I/R treatment markedly induced HT22 cell Apoptosis and ROS production, and reduced p-AKT and Bcl-2 expressions. L-NBP treatment markedly up-regulated p-AKT and Bcl-2 levels, restrained cell Apoptosis, and reduced ROS content in TH22 cells intervened by I/R. LY294002 apparently attenuated the protective effect of L-NBP on HT22 cells.

Conclusions: L-NBP protects VD by up-regulating PI3K/Akt signaling pathway, elevating Bcl-2 expression, reducing nerve cell Apoptosis, and restraining ROS production.