Abstract

Traditional Chinese medicine (TCM) plays a synergistic and comprehensive pharmacodynamic role of multi-channel and multi-target through its multi-components, showing unique therapeutic advantages in chronic and multi-gene complex diseases. Herb pair is a unique combination of two relatively fixed herbs, which embodies the integrity of TCM theory. In this study, untargeted fecal metabolomics based on MS was used to investigate the action mechanism of Radix ginseng and Schisandra chinensis (GS) herb pair on the complex disease of Alzheimer's disease (AD), and further analyze the therapeutic effects of small molecular components and saccharides of GS on AD. Quantitative analysis of bile acids (BAs) and short-chain fatty acids (SCFAs) further verified the conclusion of untargeted metabolomics. The results of the pharmacodynamics evaluation showed that the AD model was successfully constructed, and each TCM group had a different degree of improvement compared with the AD group. PCA analysis based on untargeted fecal metabolomics showed that the metabolic disorders in AD rats changed significantly over time, and there were different degrees of callback in each TCM group. The result indicated that the GS herb pair can regulate metabolic disorders of AD. Further analysis of therapeutic biomarkers showed that GS mainly regulated the metabolism of bile acid biosynthesis, sphingolipid metabolism, porphyrin and chlorophyll metabolism, etc. to treat AD. This study will help to further understand the pathogenesis of AD from metabolomics, and provide beneficial support for the further study of GS and the clinical treatment of complex diseases with TCM.

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