The permeability and efflux of Vinca alkaloids in a Caco-2 cell model

Abstract

Vinca alkaloids are used extensively in the treatment of various diseases and despite their usefulness, drug resistance, attributed to a number of mechanisms associated with the multidrug-resistance phenotype including overexpression of P-glycoprotein (P-gp), remains a serious clinical problem. To identify the possible role of P-gp on the intestinal permeability of anti-arrhythmic crude alkaloids (Vingerbine) from Vinca herbaceae, Caco-2 cells were used in this study. The four Vingerbine constituent alkaloids were analyzed by high performance liquid chromatography (HPLC). Transport parameters, permeability coefficients and percent transports were calculated. Vingerbine constituent alkaloids displayed the identical tendency but with dissimilar degree of modulation in absorptive transport direction. Vincarine and Herbadine demonstrated higher-level intestinal transcellular efflux; the co-presence of verapamil, the absorptive transport of alkaloids increased, while the secretory decreased. No asymmetric permeation was observed for Herbamine and Vincamajine. The study suggests the involvement for multidrug resistance-associated proteins (MRPs) in the intestinal transcellular efflux of Vincarine and Herbadine. The further studies will be focused upon the screening appropriate nanomedicine-based strategies to combat MDR and thus improve intestinal absorption of anti-arrhythmic alkaloids.&nbsp