title: Amelioration of cognitive impairments in APPswe/PS1dE9 mice is associated with metabolites alteration induced by total salvianolic acid.
abstract: OBJECTIVE
  Total salvianolic acid (TSA) is extracted from salvia miltiorrhiza; however, to date, there has been limited characterization of its effects on metabolites in Alzheimer's disease model-APPswe/PS1dE9 mice. The main objective of this study was to investigate the metabolic changes in 7-month-old APPswe/PS1dE9 mice treated with TSA, which protects against learning and memory impairment.
  
  
  METHODS
  APPswe/PS1dE9 mice were treated with TSA (30 mg/kg·d and 60 mg/kg·d, i.p.) and saline (i.p.) daily from 3.5 months old for 14 weeks; saline-treated (i.p.) WT mice were included as the controls. The effects of TSA on learning and memory were assessed by a series of behavioral tests, including the NOR, MWM and step-through tasks. The FBG and plasma lipid levels were subsequently assessed using the GOPOD and enzymatic color methods, respectively. Finally, the concentrations of Aβ42, Aβ40 and metabolites in the hippocampus of the mice were detected via ELISA and GC-TOF-MS, respectively.
  
  
  RESULTS
  At 7 months of age, the APPswe/PS1dE9 mice treated with TSA exhibited an improvement in the preference index (PI) one hour after the acquisition phase in the NOR and the preservation of spatial learning and memory in the MWM. Treatment with TSA substantially decreased the LDL-C level, and 60 mg/kg TSA decreased the CHOL level compared with the plasma level of the APPswe/PS1dE9 group. The Aβ42 and Aβ40 levels in the hippocampus were decreased in the TSA-treated group compared with the saline-treated APPswe/PS1dE9 group. The regulation of metabolic pathways relevant to TSA predominantly included carbohydrate metabolism, such as sorbitol, glucose-6-phosphate, sucrose-6-phosphate and galactose, vitamin metabolism involved in cholecalciferol and ascorbate in the hippocampus.
  
  
  CONCLUSIONS
  TSA induced a remarkable amelioration of learning and memory impairments in APPswe/PS1dE9 mice through the regulation of Aβ42, Aβ40, carbohydrate and vitamin metabolites in the hippocampus and LDL-C and CHOL in the plasma.
authors.affiliation: Clinical Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Zhengmin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Mingwei
authors.identifier: http://orcid.org/0000-0001-7782-1673
authors.initials: M
authors.lastname: Wang
mesh_terms: D000475:Alkenes / Q000627:therapeutic use*; D016564:Amyloid beta-Protein Precursor / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003072:Cognition Disorders / Q000097:blood / Q000188:drug therapy; D060825:Cognitive Dysfunction / Q000097:blood* / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D008401:Gas Chromatography-Mass Spectrometry; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059808:Polyphenols / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D000475:Alkenes; D016564:Amyloid beta-Protein Precursor; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D059808:Polyphenols; D014280:Triglycerides; C568740:salvianolic acid