Absorption mechanism of ginsenoside compound K and its butyl and octyl ester prodrugs in Caco-2 cells.

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.

Citation

Bing Zhang, Xue-Mei Zhu, Jiang-Ning Hu, Hui Ye, Ting Luo, Xiao-Ru Liu, Hong-Yan Li, Wei Li, Yi-Nan Zheng, Ze-Yuan Deng. Absorption mechanism of ginsenoside compound K and its butyl and octyl ester prodrugs in Caco-2 cells. Journal of agricultural and food chemistry. 2012 Oct 17;60(41):10278-84

Mesh Tags

Substances

PMID: 23013417

search → result