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.

Synthesis and pharmacokinetic characterization of a pH-sensitive polyethylene glycol ginsenoside CK (PEG-CK) conjugate

“…6) It has been reported that esterification increases pharmacokinetic properties. Fatty acid esterification of CK increases its absorption and bioavailability, 7) and has a considerable effect on its cytotoxicity against various human cancer cell lines. Although improved efficacies of various ginsenosides has been reported, 8) difficulties in target-based delivery of ginsenosides to tumor sites as well as their poor bioavailability, absorption, and solubility remain major drawbacks to the use of ginsenosides in clinical trials.…”

Alleviating the Intestinal Absorption of Rhein in Rhubarb through Herb Compatibility in Tiaowei Chengqi Tang in Caco‐2 Cells

“…Verapamil and MK-571 are well-known as the inhibitors of P-gp and MRP2, respectively [20]. Ko143, a potent and selective BCRP inhibitor, displays higher than 200-fold selectivity over P-gp and MRP1 transporters [21].…”

Effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after oral administration

“…Ginsenosides are a good substrate for P-gp [26], [27], and it is possible that B-complex vitamins could have enhanced the expression levels of P-gp in intestines, which led to the poorer absorption of ginsenoside Re. Some studies have suggested that the transport mechanism of ginsenosides is passive diffusion [19], [28]; by contrast, the main transport mechanism of B vitamins is active transport [29], [30]. However, because both passive diffusion and active transport require a specific carrier protein, it is possible that B-complex vitamins might interfere in the role of carrier protein of ginsenoside Re.…”