Analysis of Metabolic Differences of Major Alkaloids From Corydalis Decumbentis Rhizoma in Normal and Gut Microbiota‐Depleted Rats Based on UPLC‐QTOF‐MS/MS

The primary active constituents in Corydalis Decumbentis Rhizoma (Xiatianwu, XTW) are isoquinoline alkaloids, which generally exhibit low oral bioavailability. This low bioavailability suggests that these compounds may be metabolized by gut microbiota prior to absorption. However, the characteristics of gut microbiota-mediated metabolism of XTW in vivo remain unclear. This study employed ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) to identify prototype compounds and metabolites of XTW in rat feces. The metabolic profiles of XTW between the control and pseudo-germ-free (GF) rats were systematically analyzed to delineate the gut microbiota-mediated metabolic profile of XTW in rat feces. In the control group, 92 compounds were identified, with 70 of them categorized as metabolites. In the pseudo-GF group, 80 compounds were identified, among which 44 compounds were categorized as metabolites. The significant reduction in metabolite diversity in the pseudo-GF group indicates that gut microbiota-mediated metabolism was suppressed. Moreover, the levels of certain prototype alkaloids and Phase I metabolites were significantly lower in the pseudo-GF group, while Phase II metabolites were compensatorily increased. The findings demonstrate that suppression of the gut microbiota alters the in vivo metabolism of XTW. These findings provide new evidence for understanding the role of gut microbiota in the metabolism of XTW.