文献类型：期刊文献

英文题名：Rapid Identification of Tanshinone IIA Metabolites in an Amyloid-beta(1-42) Induced Alzherimer's Disease Rat Model using UHPLC-Q-Exactive Qrbitrap Mass Spectrometry

作者：Liang, Shuang[1];Wang, Zijian[2];Yuan, Jiaqi[1];Zhang, Jing[1];Dai, Xueling[3];Qin, Fei[3];Zhang, Jiayu[4];Sun, Yaxuan[3]

第一作者：Liang, Shuang

通讯作者：Sun, YX[1]

机构：[1]Beijing Union Univ, Coll Biochem Engn, Beijing 100191, Peoples R China;[2]Beijing Univ Chinese Med, Beijing Res Inst Chinese Med, Beijing 100191, Peoples R China;[3]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China;[4]Binzhou Med Univ, Sch Pharm, Yantai 264003, Peoples R China

第一机构：北京联合大学生物化学工程学院

通讯机构：[1]corresponding author), Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China.|[1141726]北京联合大学生物化学工程学院;[11417]北京联合大学;[114172]北京联合大学应用文理学院;

年份：2019

卷号：24

期号：14

外文期刊名：MOLECULES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000482303000067)】；

基金：The work was financially supported by Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University (LDSP201804); Beijing Municipal Outstanding Talent Training Funding (2015000020124G049); Premium Funding Project for Academic Human Resources Development in Beijing Union University (BPHR2018DZ03).

语种：英文

外文关键词：Tanshinone IIA; Alzheimer's disease; UHPLC-Q-Exactive Qrbitrap mass spectrometry; metabolic pathway; hippocampus; rat model; Morris water maze test; passive avoidance test

摘要：Alzheimer's disease (AD) is a neurodegenerative disorder that damages health and welfare of the elderly, and there has been no effective therapy for AD until now. It has been proved that tanshinone IIA (tan IIA) could alleviate pathological symptoms of AD via improving non-amyloidogenic cleavage of amyloid precursor protein, decreasing the accumulations of p-tau and amyloid-beta(1-42) (A beta(1-42)), and so forth. However, the further biochemical mechanisms of tan IIA are not clear. The experiment was undertaken to explore metabolites of tan IIA in AD rats induced by microinjecting A beta(1-42) in the CA1 region of hippocampus. AD rats were orally administrated with tan IIA at 100 mg/kg weight, and plasma, urine, faeces, kidney, liver and brain were then collected for metabolites analysis by UHPLC-Q-Exactive Qrbitrap mass spectrometry. Consequently, a total of 37 metabolites were positively or putatively identified on the basis of mass fragmentation behavior, accurate mass measurements and retention times. As a result, methylation, hydroxylation, dehydration, decarbonylation, reduction reaction, glucuronidation, glycine linking and their composite reactions were characterized to illuminate metabolic pathways of tan IIA in vivo. Several metabolites presented differences in the distribution of tan IIA between the sham control and the AD model group. Overall, these results provided valuable references for research on metabolites of tan IIA in vivo and its probable active structure for exerting neuroprotection.