Abstract
Alzheimer’s disease (AD) is a degenerative disease of the central nervous system characterized by the progressive impairment of neural activity. Studies have shown that 3,6′-disinapoyl sucrose (DISS) can alleviate the pathological symptoms of AD through the activation of the cAMP/CREB/BDNF signaling pathway. However, the exact biochemical mechanisms of action of DISS are not clear. This study explores metabolism of DISS in an AD mouse model, induced by the microinjection of a lentiviral expression plasmid of the APPswe695 gene into CA1 of the hippocampus. After gavage administration of DISS (200 mg/kg), the kidneys, livers, brains, plasma, urine, and feces were collected for UHPLC–Orbitrap mass spectrometry analysis. Twenty metabolites, including the prototype drug of DISS, were positively or tentatively identified based on accurate mass measurements, characteristic fragmentation behaviors, and retention times. Thus, the metabolic pathways of DISS in AD mice were preliminarily elucidated through the identification of metabolites, such as ester bond cleavage, demethoxylation, demethylation, and sinapic acid-related products. Furthermore, differences in the in vivo distribution of several metabolites were observed between the model and sham control groups. These findings can provide a valuable reference for the pharmacological mechanisms and biosafety of DISS.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that occurs mostly in the elderly and is characterized by insidious onset and slow but irreversible progression
Recognition, and short-term memory capability of the experimental mice was determined by the recognition index (RI: the ratio of the time that the mice spontaneously explored novel objects to the total time) [29]
The escape latency of the two groups gradually decreased, but the escape latency of the model group was always longer than that of the sham control group, and there was a significant difference in the escape latency between the two groups within 4 days of training (p < 0.05, Figure 3A)
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that occurs mostly in the elderly and is characterized by insidious onset and slow but irreversible progression. The pathology of AD is characterized by insoluble plaques resulting from an accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tangles. These pathologies can contribute to impaired memory and cognition, resulting in severe mental decline and behavioral abnormalities that negatively impact quality of life [1,2]. Numerous studies have shown that APP was associated with AD. In aging astrocytes and hippocampal neurons, the accumulation of mutant APP and Aβ induced mitochondrial malfunction, and abnormal neuronal autophagy, resulting in neuronal death and cognitive decline [6,7]. An AD model was generated by injecting an APPswe[695] gene lentiviral expression plasmid into the CA1 region of mice hippocampi
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