title: The effect of ethyl acetate extract from persimmon leaves on Alzheimer's disease and its underlying mechanism.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University. Shenyang 110016, China; Anhui Institute of Food and Drug Control, Hefei 230022, China.
authors.forename: Shun-Wang
authors.initials: SW
authors.lastname: Huang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University. Shenyang 110016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Meng-Yu
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University. Shenyang 110016, China.
authors.forename: Qing-Bo
authors.initials: QB
authors.lastname: Liu
authors.affiliation: China. Anhui Academy of Medical Sciences, Hefei, 230061, China.
authors.forename: Sheng-Yong
authors.initials: SY
authors.lastname: Luo
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Anhui Institute of Food and Drug Control, Hefei 230022, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
authors.affiliation: Anhui University of Chinese Medicine, Hefei 230012, China. Electronic address: dlwu7375@sina.com.
authors.forename: De-Ling
authors.initials: DL
authors.lastname: Wu
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University. Shenyang 110016, China. Electronic address: songsj99@163.com.
authors.forename: Shao-Jiang
authors.initials: SJ
authors.lastname: Song
mesh_terms: D000085:Acetates; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D016229:Amyloid beta-Peptides; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D029788:Diospyros / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde; D018782:Maze Learning / Q000187:drug effects; D008845:Microinjections; D010446:Peptide Fragments; D010936:Plant Extracts / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000085:Acetates; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010936:Plant Extracts; D012997:Solvents; C075222:amyloid beta-protein (1-42); D008315:Malondialdehyde; C007650:ethyl acetate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Alzheimer's disease; Apoptosis; Ethyl acetate extract of persimmon leaves; JNK signaling pathway