Metabolomics is the comprehensive assessment of endogenous metabolites of a biological system in a holistic context, and its property consists with the global view of traditional Chinese medicine (TCM). Suanzaoren decoction (SZRD), an ancient TCM formulae, has been used for treating insomnia for centuries, and its mechanism remains unclear completely. This paper was designed to explore globally metabolomic characters of the insomnia and the therapeutic effects of SZRD. Ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) combined with pattern recognition approaches including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA) were integrated to approximate the comprehensive metabolic signature and discover differentiating metabolites. The changes in metabolic profiling were restored to their baseline values after SZRD treatment according to the PCA score plots. Altogether, the current metabonomic approach based on UPLC/ESI-SYNAPT-HDMS indicate 20 ions (9 in the negative mode, 11 in the positive mode) as "differentiating metabolites". The alterations in these metabolites were associated with perturbations in amino acid and fatty acid metabolism, in response to insomnia through immune and nervous system. Of note, we found that SZRD increases sleep activity and exhibits binding affinity for serotonin receptors. These results implicate the therapeutic effects of SZRD may mediate through serotonergic activation. Our findings also show the robust UPLC/ESI-SYNAPT-HDMS techniques is promising for metabolites profiling analysis of TCM and open new perspectives to using metabolomics platform to resolve special TCM issues.
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