title: Metabolomics approach to explore the effects of Kai-Xin-San on Alzheimer's disease using UPLC/ESI-Q-TOF mass spectrometry.
abstract: Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that influences elderly populations, with no effective method for its treatment so far. To improve its diagnosis and treatment, changes of small molecule metabolite during AD should be elucidated. Kai-Xin-San (KXS) is an herbal formulae that has been widely used to treat mental disorders, especially amnesia and depression in China. Experimental AD was induced in rats by an intraperitoneal injection of d-galactose (d-gal) and administered intragastrically with aluminum chloride (AlCl3) simultaneously for 105 days. Morris water maze task as a behavior test was used for testing the effects of KXS on AD model and pathological changes to the brain were assessed by hematoxylin-eosin staining and immunohistochemistry. The levels of Bcl-2 and ChAT in hippocampus were evaluated by western-blot. Furthermore, metabolite profiling of AD was performed through ultra-performance liquid chromatography/electrospray ionization quadruple time-of- flight-high-definition mass spectrometry (UPLC/ESI-Q-TOF/HDMS) combined with pattern recognition approaches and pathway analysis. d-gal and AlCl3-treated caused a decline in spatial learning and memory, hippocampal histopathological abnormalities and increased Aβ1-40 levels in the brain cortex and hippocampus along with decreased Bcl-2 and ChAT expression in the hippocampus. KXS significantly improved the cognitive impairment induced by d-gal and AlCl3, attenuated hippocampal histopathological abnormalities, reduced Aβ1-40 levels and increased Bcl-2 and ChAT expression in the hippocampus. A total of 48 metabolites were considered as potential biomarkers of AD, and 36 metabolites may correlate with the regulation of KXS treatment on AD. Changes in AD metabolic profiling were close to normal states through regulating multiple perturbed pathways after KXS treatment. This study has revealed the potential biomarkers and metabolic networks of AD, illuminated the biochemistry mechanism of AD and the metabolic pathways influenced by KXS.
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Chu
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors.forename: Shengwen
authors.initials: S
authors.lastname: Lu
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Kong
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Han
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Sino-America Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Key Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China. Electronic address: wangxijunomics@126.com.
authors.forename: Xijun
authors.initials: X
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000737:chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D004365:Drugs, Chinese Herbal; C000605449:Kai-Xin-San
keywords: Alzheimer’s disease; Kai-Xin-San; Metabolomics; SYNAPT G2-Si HDMS; Traditional chinese medicine