The effect of ethyl acetate extract from persimmon leaves on Alzheimer's disease and its underlying mechanism.
BACKGROUND Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by neuronal loss in the brain and cognitive impairment. AD is now considered to be the third major cause of death in developed countries, after cardiovascular disease and cancer. Persimmon leaves are used as a popular folk medicine to treat hypertension, angina and internal haemorrhage in Cyangbhina, and it has been reported that ethyl acetate extract of persimmon leaves (EAPL) displays a potential therapeutic effect on neurodegenerative diseases. HYPOTHESIS/PURPOSE 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. STUDY DESIGN AD model was established by bilateral injection of Ab1 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. RESULTS EAPL at doses of 200mg/kg, 400mg/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. CONCLUSION The results indicate that EAPL has a potent protective effect on cognitive deficits induced by Ab 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.
Phytomedicine international journal of phytotherapy and phytopharmacology