Unraveling corilagin's absorption and metabolism: a multimodal approach

Corilagin is an ellagitannin, a natural product found in a wide variety of foods, but its absorption and utilization process in the mammalian intestine is still unclear. A combination of the everted intestinal sac method (in vitro), the Ussing chamber technique (ex vivo), and animal experiment (in vivo) was used to study the pharmacokinetic profile and intestinal segmental absorption and metabolism of corilagin. We have further established a new method for digesting corilagin in the presence or absence of gut microbiota by using endogenous enzymes from intestinal epithelial cells. The experimental results showed that corilagin is rapidly absorbed in rats, reaching peak concentration (C_max = 87.64 ng mL^-1) 2 h after oral administration, with a half-life of 7.94 ± 4.09 h. In the everted intestinal sac model, the jejunum exhibited the highest absorption capacity for corilagin, while in the Ussing chamber model, the duodenum was the primary absorption site. Corilagin can be metabolized into trans-2-butene-1,4-dicarboxylic acid, 1-galloyl-β-glucose, pyrogallol, and dimethyl ellagic acid. In addition, the endogenous enzyme metabolite gallic acid can be continuously utilized by gut microbiota, as observed through the new method. Moreover, 83 differential metabolites were detected by extensive targeted metabolomics analysis. These findings clarify the absorption and biotransformation pathways of corilagin in experimental models, thereby providing mechanistic insights into the intestinal metabolism of corilagin.