Strategies for determining the bioactive ingredients of honey‐processed Astragalus by serum pharmacochemistry integrated with multivariate statistical analysis

Abstract Honey‐processed Astragalus is a widely used traditional Chinese medicine that has a better effect on reinforcing “Qi” (vital energy) than the raw one. A comparative study of metabolites analysis between them in rat serum for finding the bioactive ingredients was carried out using serum pharmacochemistry and multivariate statistical analysis. The blood collection methods and time were optimized first. Then the prototypes and metabolites in serum samples after oral administration were investigated by ultra‐high‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight mass spectrometry integrated with principal component analysis and orthogonal partial least squares discriminant analysis. The contents of metabolites were also analyzed to evaluate the metabolic profile differences. As a result, nine prototypes and 36 metabolites were identified. Only two prototypes and 15 metabolites were different between raw and honey‐processed Astragalus . Their biotransformation reactions contained the process of oxidation, demethylation, and hydrolysis in phase I and glucuronide conjugation or sulfate conjugation in phase II. Most of the detected metabolites were transformed from isoflavones and isoflavanes. Our results expand the knowledge about the influence of honey‐processing on Astragalus and suggest the different curative effects between raw and honey‐processed Astragalus might due to their therapeutic material discrepancy.