title: Absorption mechanism of ginsenoside compound K and its butyl and octyl ester prodrugs in Caco-2 cells.
abstract: Ginsenoside compound K (CK) is a bioactive compound with poor oral bioavailability due to its high polarity, while its novel ester prodrugs, the butyl and octyl ester (CK-B and CK-O), are more lipophilic than the original drug and have an excellent bioavailability. The aim of this study was to examine the transport mechanisms of CK, CK-B, and CK-O using human Caco-2 cells. Results showed that CK had a low permeability coefficient (8.65 × 10(-7) cm/s) for apical-to-basolated (AP-BL) transport at 10-50 μM, while the transport rate for AP to BL flux of CK-B (2.97 × 10(-6) cm/s) and CK-O (2.84 × 10(-6) cm/s) was significantly greater than that of CK. Furthermore, the major transport mechanism of CK was found as passive transcellular diffusion with active efflux mediated by P-glycoprotein (P-gp). In addition, it was found that CK-B and CK-O were not the substrate of efflux transporter since the selective inhibitors (verapamil and MK-571) of efflux transporter had little effects on the transport of CK-B and CK-O in the Caco-2 cells. These results suggest that improving the lipophilicity of CK by acylation can significantly improve the transport across Caco-2 cells.
authors.affiliation: State Key Laboratory of Food Science and Technology, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhu
authors.forename: Jiang-Ning
authors.initials: JN
authors.lastname: Hu
authors.forename: Hui
authors.initials: H
authors.lastname: Ye
authors.forename: Ting
authors.initials: T
authors.lastname: Luo
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Liu
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Zheng
authors.forename: Ze-Yuan
authors.initials: ZY
authors.lastname: Deng
mesh_terms: D000042:Absorption; D000215:Acylation; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D036145:Ginsenosides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D005894:Panax; D011355:Prodrugs / Q000378:metabolism / Q000493:pharmacokinetics*; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014700:Verapamil / Q000494:pharmacology
chemical_list: D036145:Ginsenosides; D011355:Prodrugs; D011422:Propionates; D011804:Quinolines; D014700:Verapamil; C059141:verlukast; C112772:ginsenoside compound K