title: A UHPLC-TOF/MS method based metabonomic study of total ginsenosides effects on Alzheimer disease mouse model.
abstract: A metabonomic method was established to find potential biomarkers and study the metabolism disturbance in Alzheimer disease animal model. Total ginsenosides, as potential agent in neuroprotection and anti-inflammation, was also studied to learn the regulation mechanism to plasma metabolites in model animals. In experiment, amyloid beta 1-42 was occupied to form Alzheimer disease animal model. After drug administration, animals were evaluated by Morris water maze behavior test and sacrificed. Plasma samples were then analyzed using UHPLC-TOF/MS method to determine the endogenous metabolites. Behavior test results revealed that the spatial learning and memory abilities were deficit in model mice, and total ginsenosides could improve cognition abilities in dose-dependent manners. Principal component analysis showed that model and sham were divided into two groups, which means the metabolic network of mice was disturbed after modeling. Accordingly, 19 biomarkers were found and identified. In model group, the levels of proline, valine, tryptophan, LPC (14:0), LPC (15:0), LPC (15:1), LPC (17:0), LPC (18:2), LPC (18:3) and LPC (20:4) were up-regulated, while the levels of acetylcarnitine, palmitoylcarnitine, vaccenylcarnitine, phytosphingosine, N-eicosanoylethanolamine, hexadecenoic acid, docosahexaenoic acid, docosapentaenoic acid and octadecadienoic acid were down-regulated. The levels of these metabolites were recovered in different degrees after total ginsenosides administration. Combining with behavior study results, total ginsenosides could ameliorate both cognition symptoms and metabolic changes in model animals. This metabonomic approach provided a feasible way to understand the endogenous alterations of AD and to study the pharmacodynamic activity of novel agents.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yingge
authors.initials: Y
authors.lastname: Gong
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road,Shenyang 110016, China. Electronic address: dixin63@hotmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Di
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: kaishunbi.syphu@gmail.com.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055432:Metabolomics / Q000295:instrumentation / Q000379:methods*; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D025341:Principal Component Analysis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods
chemical_list: D015415:Biomarkers; D036145:Ginsenosides; D018696:Neuroprotective Agents
keywords: Alzheimer disease; Animal model; Biomarkers; Metabonomics; Total ginsenosides