title: Icariin decreases the expression of APP and BACE-1 and reduces the β-amyloid burden in an APP transgenic mouse model of Alzheimer's disease.
abstract: OBJECTIVE
  The purpose of this study was to investigate the effects and pharmacological mechanisms of icariin, which is the main component in the traditional Chinese herb Epimedium, on β-amyloid (Aβ) production in an amyloid precursor protein (APP) transgenic (Tg) mouse model of Alzheimer's disease (AD).
  
  
  METHODS
  APPV717I Tg mice were randomly divided into a model group and icariin-treated (30 and 100 μmol/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition tests. Aβ contents were measured by enzyme-linked immunosorbent assays and immunohistochemistry. Amyloid plaques were detected by Congo red staining and Bielschowsky silver staining. The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry.
  
  
  RESULTS
  Ten-month-old Tg mice showed obvious learning-memory impairments, and significant increases in Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus.
  
  
  CONCLUSIONS
  Icariin reduced the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the APP and BACE-1 levels. These novel findings suggest that icariin may be a promising treatment in patients with AD.
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007859:Learning Disabilities / Q000188:drug therapy / Q000378:metabolism; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000188:drug therapy*
chemical_list: D016564:Amyloid beta-Protein Precursor; D005419:Flavonoids; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; C056599:icariin
keywords: APPV717I transgenic mice; Alzheimer's disease; BACE-1; Icariin; amyloid plaque; amyloid precursor protein; β-amyloid