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Transport properties of Ginkgolides C, J and Bilobalide in Caco-2 and MDR-MDCK monolayer models
In this study intestinal and BBB transport of three terpene lactones (ginkgolide C, ginkgolide J and bilobalide), isolated from Ginkgo biloba (Family-Ginkgoaceae), was evaluated in Caco-2 and MDR-MDCK cell monolayer models. Transepithelial transport was examined for 2 hours in both absorptive and secretory directions. Quantitation of terpene lactones was performed by UPLC-MS. In the Caco-2 model, each compound (100µM) displayed a pH-dependent transport in the absorptive direction. The transport in the secretory direction was higher for all three compounds at physiological pH and efflux ratio was in the range of 1.7–2.4. Permeability of bilobalide (Papp 2×10-6 cm/s) was much higher than that of ginkgolide C (Papp1.2×10-6 cm/s) and ginkgolide J (Papp 0.7 10-6 cm/s) across Caco-2 monolayer. In the MDR-MDCK model, a low permeability was observed in the absorptive direction (Papp 0.2–0.3×10-6 cm/s) while in secretory direction the flux was much higher (Papp 2.9–3.6×10-6 cm/s). The TEER values of the monolayers were within the range of 400–600 and 1200–1600 ohm.cm2 for Caco-2 and MDR-MDCK monolayers, respectively.
In conclusion, absorption of ginkgolide C, J and bilobalide in Caco-2 cells was pH-dependent. A poor absorption across MDR-MDCK monolayers was observed. Other methods like the in vivo mouse brain uptake assay or in situ models may be more useful to characterize their transport properties across BBB.