title: Enhancement of intestinal absorption of akebia saponin D by borneol and probenecid in situ and in vitro.
abstract: Akebia saponin D is a typical bioactive triterpenoid saponin isolated the rhizome of Dipsacus asper Wall. Our previous studies demonstrated that the oral bioavailability of akebia saponin D was very low, but the underlying mechanisms remained unknown. The present study aims to investigate the intestinal absorptive characteristics of akebia saponin D as well as the absorptive transport behavior influenced by co-administration of three absorption-enhancing agents and three efflux protein inhibitors using an in vitro everted gut sac method and an in situ intestinal perfusion model. The results showed that akebia saponin D had a quite limited intestinal permeability, and there was a non-linear increase in transepithelial transportation with increasing concentrations of akebia saponin D. The absorption of akebia saponin D was intestinal segment selective and the small intestine was the best absorptive site. Among three absorption promoters, borneol could significantly improve the permeability of akebia saponin D across ileum, while Tween-80 and DMSO had almost no absorption-enhancing effect. In addition, verapamil, probenecid and pantoprazole in the perfusates were used in this study as modulators of transporters such as P-glycoprotein, MRPs and BCRP in the intestinal mucosa, respectively. The results exhibited that the ileal permeability of akebia saponin D was markedly elevated by the co-administration of probenecid, indicating that akebia saponin D may be likely a substrate of MRPs. The above-mentioned results suggest that akebia saponin D has a poor intestinal absorption not only due to its poor transepithelial permeability but also owing to the contribution of efflux transporters such as MRPs in the intestine.
authors.affiliation: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Ministry of Education, Nanjing 210009, PR China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Weize
authors.initials: W
authors.lastname: Li
authors.forename: Lvyi
authors.initials: L
authors.lastname: Chen
authors.forename: Shuwei
authors.initials: S
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Ping
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Yang