Origin-dependent metabolic variations: How Atractylodes macrocephalae Rhizoma extract’s chemical diversity leads to stage-specific changes in simulated digestion

Atractylodes macrocephalae Rhizoma (AMR), a traditional Chinese medicine, is extensively utilized in clinical practice for its pharmacological properties, including anti-inflammatory, anti-tumor, and gastrointestinal regulatory effects. Nonetheless, the intricate nature of traditional Chinese medicine extracts has resulted in few studies into the effects of compositional variations in Atractylodes macrocephalae Rhizoma extracts (AMRE) from diverse sources on gastrointestinal metabolic processes. This study developed an integrated in vitro and in vivo compound analysis strategy utilizing Ultrahigh-performance liquid chromatography Quadrupole-Orbitrap tandem mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) and the Simulator of Human Intestinal Microbial Ecosystem (SHIME) to examine the metabolic alterations caused by variations in the chemical constituents of AMRE from diverse sources. A total of 117 chemical constituents were found, primarily classified as terpenoids, organic acids, alkaloids, coumarins, and phenylpropanoids. 51 prototype components and 79 metabolites were identified. The metabolic processes were predominantly observed among terpenoids, with reaction types encompassing hydroxylation, oxidation, hydrogenation, methylation, glucuronidation, and sulfonation. Analysis of dynamic changes revealed that the majority of the prototype components underwent a considerable reduction in the colon, while the metabolites were markedly enriched in both the small intestine and colon. Differential analysis showed that AMRE3 contained the highest number of terpenoid compounds, AMRE1 exhibited the highest average content of chemical constituents, and AMRE2 had the lowest. These disparities were consistently observed in both prototype components and metabolic behaviors, thereby affirming the robust correlation between metabolite distribution and chemical constituents. This study elucidates, for the first time, the variations in the chemical constituents of AMRE from diverse sources and the metabolic characteristics and discrepancies they elicit in the human gastrointestinal tract (GI tract), offering a viable strategy for further clarifying the material basis of its pharmacological effects and clinical applications.