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Rapid Identification of Tanshinone IIA Metabolites in an Amyloid-β1-42 Induced Alzherimer’s Disease Rat Model using UHPLC-Q-Exactive Qrbitrap Mass Spectrometry

1
College of Biochemical Engineering, Beijing Union University, Beijing 100191, China
2
Beijing University of Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing 100191, China
3
Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China
4
School of Pharmacy, Binzhou Medical University, Yantai 264003, China
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(14), 2584; https://doi.org/10.3390/molecules24142584
Received: 14 June 2019 / Revised: 8 July 2019 / Accepted: 9 July 2019 / Published: 16 July 2019
(This article belongs to the Section Analytical Chemistry)
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-β1–42 (Aβ1–42), 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 Aβ1-42 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. View Full-Text
Keywords: Tanshinone IIA; Alzheimer’s disease; UHPLC-Q-Exactive Qrbitrap mass spectrometry; metabolic pathway; hippocampus; rat model; Morris water maze test; passive avoidance test Tanshinone IIA; Alzheimer’s disease; UHPLC-Q-Exactive Qrbitrap mass spectrometry; metabolic pathway; hippocampus; rat model; Morris water maze test; passive avoidance test
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MDPI and ACS Style

Liang, S.; Wang, Z.; Yuan, J.; Zhang, J.; Dai, X.; Qin, F.; Zhang, J.; Sun, Y. Rapid Identification of Tanshinone IIA Metabolites in an Amyloid-β1-42 Induced Alzherimer’s Disease Rat Model using UHPLC-Q-Exactive Qrbitrap Mass Spectrometry. Molecules 2019, 24, 2584. https://doi.org/10.3390/molecules24142584

AMA Style

Liang S, Wang Z, Yuan J, Zhang J, Dai X, Qin F, Zhang J, Sun Y. Rapid Identification of Tanshinone IIA Metabolites in an Amyloid-β1-42 Induced Alzherimer’s Disease Rat Model using UHPLC-Q-Exactive Qrbitrap Mass Spectrometry. Molecules. 2019; 24(14):2584. https://doi.org/10.3390/molecules24142584

Chicago/Turabian Style

Liang, Shuang; Wang, Zijian; Yuan, Jiaqi; Zhang, Jing; Dai, Xueling; Qin, Fei; Zhang, Jiayu; Sun, Yaxuan. 2019. "Rapid Identification of Tanshinone IIA Metabolites in an Amyloid-β1-42 Induced Alzherimer’s Disease Rat Model using UHPLC-Q-Exactive Qrbitrap Mass Spectrometry" Molecules 24, no. 14: 2584. https://doi.org/10.3390/molecules24142584

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