Qualitatively and quantitatively investigating the metabolism of 20(S)‐protopanaxadiol‐type ginsenosides by gut microbiota of different species

Abstract Ginsenosides Rb1, Rb2, Rb3 and Rc, four major protopanaxadiol (PPD)‐type ginsenosides, can be metabolized by gut microbiota. The composition of gut microbiota varies in different species. Existing publications have reported the metabolite fates of ginsenosides by gut microbiota from single species. However, their microbiota‐related metabolic species differences have not been evaluated yet. In current study, in vitro anaerobic incubations of PPD‐type ginsenosides with gut microbiota from humans, rabbits and rats were conducted. The metabolites of each ginsenoside were then identified by LC–MS. A total of 15 metabolites from the four ginsenosides were identified. The major metabolic pathways were stepwise removals of the C‐20 and C‐3 sugar moieties to obtain aglycone PPD. The results showed that the hydrolysis rate of C‐20 terminal β ‐D‐glucopyranosyl was significantly higher than those of α ‐L‐arabinopyranosyl, β ‐D‐xylopyranosyl and α ‐L‐arabinofuranosyl in different species. The activity of β ‐glucosidase, the metabolic rates of parent compounds and the formation rates of their metabolites were significantly higher in gut microbiota from rabbits than from humans and rats. Our research draws researchers’ attention to the species differences of microbiota‐related drug metabolism.