Abstract
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.
Highlights
Alzheimer’s disease (AD) is an overwhelming neurodegenerative disorder that weakens the mental, memorial and cognitional ability of patients, eventually leading to death due to infectious diseases and pneumonia [1]
Total ion chromatograms of urine, feces, heart, liver, kidney, brain and plasma samples, which ion from chromatograms of urine, feces, liver, kidney, brain plasma samples, which were Total collected experimental rats after oralheart, administration of tanshinone IIA (tan IIA),and were analyzed by Thermo were collected from experimental ratsthe after oral administration of tan IIA, analyzed by Thermo
Tan IIA was suspended in 0.5% sodium carboxymethyl cellulose (CMC-Na) solution, and the rats of the sham control group and the model group were orally administered with a dose of 100 mg/kg weight
Summary
Alzheimer’s disease (AD) is an overwhelming neurodegenerative disorder that weakens the mental, memorial and cognitional ability of patients, eventually leading to death due to infectious diseases and pneumonia [1]. It has been proved that tan IIA exerts antitumor [17,18], anti-inflammatory [19,20], and so forth. IIA exerts significant neuroprotective effects via various mechanisms. Orbitrap mass spectrometry is a qualitied technique for ion fragmentation scanning with high sensitivity, resolving power and mass accuracy [29] and has been comprehensively used in these fields such as metabolomics, proteomics, lipidomics, and so forth [30,31,32]. This study, firstly applied an UHPLC-Q-Exactive Qrbitrap mass spectrometry-based method to explore tan IIA metabolites in an AD rat model, which was significant to understand the underlying mechanisms of neuroprotective effect of tan IIA against AD. Test was appliedQrbitrap to examine learning and memory capability explore tan metabolites in an rat model, which was significant to understand the underlying experimental rats.
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