Serum lipidomics study of Ding-Zhi-Xiao-Wan effect on Alzheimer's disease using online liquid extraction surface analysis coupled to direct infusion mass spectrometry

Disorder of lipid metabolism is closely related to the incidence of Alzheimer's disease (AD). Regulation of lipid disorder is one of the important mechanisms of drug therapy for AD. In this study, serum lipidomics study based on an online liquid extraction surface analysis coupled to direct infusion mass spectrometry (Online-LESA-direct infusion MS) was established and applied to assess the efficacy of Ding-Zhi-Xiao-Wan (DZXW) for treating AD in rats by regulating lipid metabolism disorders. Dried serum spot (DSS) samples of 10 health control (HG), 10 AD, 10 DZXW, and 10 donepezil rats were directly detected by Online-LESA-direct infusion MS without prior treatments. And the acquired data was analyzed by multivariate statistical analyses such as PCA and PLS-DA to identify potential lipid biomarkers in serum. By this method, 15 compounds were screened and identified, belonging to phosphatidylcholines (PCs), sphingomyelins (SMs) and lysophosphatides (LPCs), which were considered as potential lipid biomarkers with AD mechanisms. Among them, the levels of PCs and SMs were markedly declined, and the levels of LPCs were increased in the AD group. Moreover, compared with administrating donepezil, the observed PCs and SMs were more up-regulation to normal levels with the treatment of DZXW in AD rats, which indicated that DZXW can play a better role in the treatment of AD by regulating lipid metabolism. And the results of the study also showed that the Online-LESA-direct infusion MS on DSS analytical strategy has a potential to become a high-throughput analysis method for large-scale clinical diagnostics analysis.