The permeability and the efflux of alkaloids of the Evodiae fructus in the Caco-2 model.

The intestinal transport of four indoloquinazoline alkaloids, rutaecarpine (RCP), evodiamine (EDM), dehydroevodiamine (DEDM) and wuzhuyurutine B (WZYB) isolated from the Evodiae fructus was investigated using the monolayers of the human colon adenocarcinoma cell line Caco-2 as a model system for intestinal absorption. The four alkaloids were measured by high performance liquid chromatography (HPLC) coupled with UV detector. Transport parameters and permeability coefficients were then calculated and compared under identical conditions with those of mannitol, propranolol and paclitaxel. Permeability coefficients were also compared with the reported values for model compounds like propranolol and mannitol. The four alkaloids at a concentration of 5 microM were demonstrated substantial transport across the Caco-2 cell monolayers with moderate to high permeability coefficients and WZYB demonstrated higher-level intestinal transcellular efflux. The transports of DEDM and WZYB were concentration dependent at the concentrations of 5-25 microM. Among four alkaloids, EDM and DEDM are better-transported compounds, and RCP and WZYB are moderate transport compounds. The data support the involvement for multidrug resistance-associated proteins (MRPs) in the intestinal transcellular efflux of WZYB. Copyright 2008 John Wiley & Sons, Ltd.