Comprehensive Evaluation of the Metabolism of Genipin-1-β-d-gentiobioside in Vitro and in Vivo by Using HPLC-Q-TOF.

To examine the metabolism of genipin-1-β-d-gentiobioside (GG), its distribution and biotransformation in vivo and in vitro were investigated. Urine, plasma, feces, and various organs were collected after oral administration of GG to normal rats and pseudo-germ-free rats to evaluate GG metabolism in vivo. GG was incubated with intestinal flora and primary hepatocytes in vitro to investigate microbial and hepatic metabolism. Using HPLC-Q-TOF-LC/MS, 11 metabolites of GG were absolutely or tentatively identified in terms possible elemental compositions, retention times, and characteristics of fragmentation patterns corresponding to eight biotransformations: deglycosylation, hydroxylation, sulfate conjugation, glucuronidation, hydrogenation, demethylation, glycosylation, and dehydration. Fewer metabolites were detected in pseudo-germ-free rats than in conventional rats. Moreover, geniposide and genipin were generated by the deglycoslation of intestinal bacteria. Geniposidic acid was detected in rat primary-hepatocyte incubation. This study first explores the metabolism of GG in vivo and in vitro. The results can aid the elucidation of PK profiles and clinical usage of gardenia fruit.