OBJECTIVE To investigate the dynamic changes of prototype components in Eucommia ulmoides granules (EUG) during the digestive process in patients with gestational diabetes mellitus (GDM) and evaluate the changes in endogenous metabolites after administration. METHODS High-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) were employed to identify the chemical constituents of EUG. Simultaneously, a simulator of human intestinal microbial ecosystem (SHIME) digestive system model was established using fecal sample from patient with GDM. Based on this model, UHPLC-MS/MS was utilized to conduct comprehensive non-targeted metabolomic analysis of digestive fluid samples from the treatment group (administered with EUG) and the control group. The difference and evolution trend of Eucommia components in different digestive parts were compared, and the categories of Eucommia were classified in detail. Finally, differences in endogenous metabolites were further compared, and pathway enrichment and correlation analyses was conducted to reveal the specific effects of EUG on metabolic pathways in the body. RESULTS A total of 55 prototype components were identified in digestive fluids, including active constituents such as geniposidic acid, chlorogenic acid, caffeic acid, baicalin, and quercetin. These components primarily belonged to flavonoids, terpenoids, lignans, phenolic acids, and phenylpropanoids. Regional analysis revealed that flavonoids and phenolic acids dominated in gastric fluids, flavonoids and lignans were significantly enriched in the small intestine, and terpenoids were predominant in the colon. Forty-five endogenous metabolites were detected, with eight showing significant differences between the treatment and control groups. These differential metabolites were strongly correlated with Eucommia prototype components. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that these metabolites were primarily involved in β-alanine metabolism, glutathione metabolism, and arginine/proline metabolism. CONCLUSION Prototype components of EUG exhibit region-specific metabolic characteristics during digestion: flavonoids and lignans are predominantly absorbed in the small intestine, while terpenoids are excreted via the colon. This study demonstrates that EUG may ameliorate GDM by modulating endogenous metabolites associated with β-alanine, glutathione, and arginine/proline metabolism pathways.

OBJECTIVE To analyze the chemical composition of the Qingfei mixture and their metabolic changes within the simulator of human intestinal microbial ecosystem(SHIME) employing SHIME and ultra highperformance liquid chromatography tandem electrostaticfield orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap MS/MS). METHODS UHPLC-MS/MS technology was utilized for mass spectrometry data acquisition of the samples, and the chemical components of the Qingfei Mixture and their metabolites within the SHIME were analyzed and identified by comparing the database and the reported fragmentation pattern of known compounds. RESULTS A total of 88 chemical components were identified in the Qingfei Mixture, comprising 41 organic acids, 9 alkaloids, 8 flavonoids, and 30 other types. In the SHIME samples, 32 prototype components and 29 metabolites were identified. CONCLUSION This study has clarified the chemical components of the Qingfei Mixture and elucidated the metabolic changes it undergoes in the SHIME, providing a scientific basis for its mechanism of action research and clinical application.

OBJECTIVE To identify the chemical constituents of Chanbei mixture and investigate the changes of simulated gastrointestinal metabolism based on the simulator of human intestinal microbial ecosystem (SHIME). METHODS The chemical constituents of Chanbei mixture and its metabolites in SHIME system were identified by ultra high performance liquid chromatography-quadrupole-orbitrap-mass spectrometer (UHPLC-Q-Orbitrap-MS/MS). RESULTS A total of 168 chemical components were identified, mainly flavonoids, coumarins, terpenoids, organic acids, alkaloids and so on. In addition, a total of 108 prototype components were detected in the SHIME system, and their metabolic processes in SHIME mainly included oxidation, reduction, hydration, methylation, demethylation, acetylation, glucuronidation, etc. CONCLUSION This study elucidates the material basis of Chanbei mixture and simulates its metabolism in human gastrointestinal simulation system. SHIME system can simulate the digestive process of oral preparations in human gastrointestinal tract, and this method can provide a reference for the study of metabolism of oral preparations in vivo.