title: Effect of Tong Luo Jiu Nao on Aβ-degrading enzymes in AD rat brains.
abstract: BACKGROUND
  Tong Luo Jiu Nao (TLJN) is a modern Chinese formula based on Traditional Chinese Medicine theory that has been used to treat ischemic cerebral stroke and vascular dementia. TLJN belongs to the ethnopharmacological family of medicines. In this study, we investigated the mechanism of the TLJN effect on Alzheimer's disease (AD).
  
  
  OBJECTIVE
  To investigate the effect of TLJN on β-amyloid-degrading enzymes and learning and memory in the AD rat brain.
  
  
  METHODS
  AD rats whose disease was induced by Aβ(25-35) injection into the bilateral hippocampus CA1 region were subjected to intragastric administration of various preparations. The experimental animals were healthy male Sprague-Dawley rats which were randomly divided into normal, sham, model, TLJN min, TLJN max and donepezil hydrochloride groups. Spontaneous alternation and passive avoidance behavior, which are regarded as measures of spatial learning and memory, were investigated using Y-maze testing. Western blotting and immunohistochemistry were used to observe the therapeutic effect of TLJN on the deposits of amyloid plaque and on the expression of synaptophysin, insulin-degrading enzyme and neprilysin.
  
  
  RESULTS
  Y-maze results showed that the AD model group presented with spatial learning and memory impairments. Hematoxylin-eosin and Congo red staining indicated neuronal impairment and deposits of amyloid plaque in the model group and these results were consistent with their learning and memory deficits in the Y-maze. The TLJN-treated groups exhibited prolonged a cavity delitescence, decreased arm entries and improvement in learning and memory. Moreover, the structure of the neurons of the treated groups was restored and the expression of synaptophysin increased in both the hippocampus and cortex. In addition, their levels of insulin-degrading enzyme and neprilysin in the cortex and hippocampus were upregulated and the amyloid plaque was decreased.
  
  
  CONCLUSIONS
  TLJN can improve learning and memory, up-regulate insulin-degrading enzyme and neprilysin levels, promote the degrading of Aβ and clear amyloid plaque from the AD rat brain. In future, TLJN may have significant therapeutic potential in the treatment of AD patients.
authors.affiliation: Department of Pathology, School of Preclinical Medicine, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Road, Chaoyang District, Beijing 100029, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Hua
authors.forename: Hongtao
authors.initials: H
authors.lastname: Lei
authors.forename: Pengtao
authors.initials: P
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007339:Insulysin / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D015260:Neprilysin / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C528243:tongluo jiunao; D015260:Neprilysin; D007339:Insulysin