This study was designed to investigate the effects of EAPL on AD, to clarify the possible mechanism by which EAPL exerts its beneficial effects and prevents AD, and to determine the major constituents involved.
AD model was established by bilateral injection of Aβ1-42 into the hippocampus of rats. The cognitive performance was determined by the Morris water maze and step-down tests. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), apoptosis, total and phosphorylated c-Jun NH2-terminal kinase (JNK/p-JNK), caspase-3, Bax and Bcl-2 were determined. In addition, a sensitive and reliable LC-QTOF-MS method was applied to identify the major compounds present in EAPL.
EAPL at doses of 200 mg/kg, 400 mg/kg could markedly reduce the latency, significantly increase the time in the first quadrant and number of the target crossing times in Morris water maze test, markedly increase the latency and reduce the number of errors in the step-down test, significantly inhibit the reductions in SOD and GSH-Px activities, and increase the level of MDA. In addition, EAPL treatment attenuated neuronal apoptosis in the hippocampus, reduced the expression of p-JNK, caspase-3, and the relative ratio of Bax/Bcl-2. Meanwhile, 32 constituents were identified by LC-QTOF-MS/MS assays.
The results indicate that EAPL has a potent protective effect on cognitive deficits induced by Aβ in rats and this effect appears to be associated with the regulation of the antioxidative defense system and the mechanism of mitochondrial-mediated apoptosis. Furthermore, analysis of the LC-MS data suggests that flavonoids and triterpenoids may be responsible for the potential biological effects of EAPL.