High-throughput lipidomics characterize key lipid molecules as potential therapeutic targets of Kaixinsan protects against Alzheimer's disease in APP/PS1 transgenic mice

Abstract

Alzheimer's disease (AD) is still a major problem nowadays. Under the circumstance of many chemical drugs have poor effects on AD, traditional Chinese medicine has become a hot spot for us due to its multi-target and multi-path advantages. To explore the potential therapeutic targets of Kaixinsan (KXS) protects against AD in APP/PS1 transgenic mice model. All mice were divided into three groups: control group, model group and KXS group. Orally given KXS from two month old, and the control and model groups were given the same dose of distilled water. We collected all mice's serum samples at the 12th month age to determine the lipid markers of AD by compare with the model and control groups in full-scan analysis based on high-throughput serum lipidomics technology. Then we found the lipid molecules called back by KXS from the KXS protects against AD. Compared with the control group, the metabolic profile of the model mice was obviously disordered, and we identified 16 lipid-related biomarkers associated with AD. After KXS treatment, the metabolic profiles of these disorders tended to recover compared with the model group. And we identified eight key lipid molecules, of which four had statistical significance. We found that the main perturbation pathways related to AD were linoleic acid metabolism, arachidonic acid metabolism and sphingolipid metabolism. All these metabolic pathways showed different degrees of rotation after KXS administration. Through the pathways analysis, we found 4 lipids molecules with significant differences, which could be used as new targets for the treatment of AD.

Keywords: APP/PS1 transgenic mice; Alzheimer's disease (AD); Kaixinsan (KXS); Lipidomics; Traditional Chinese medicine.