Black ginger extract and its active compound, 5,7-dimethoxyflavone, increase intestinal drug absorption via efflux drug transporter inhibitions.

Black ginger is used as an herbal medicine for self-care and health promotion. Black ginger extract has been shown to alter the function of transporters in several cell types. This study demonstrates the interaction between the extract and 5,7-dimethoxyflavone (DMF) on drug efflux mediated by breast cancer resistance proteins (BCRP) and P-glycoprotein (P-gp) in Caco-2 cells and heterologous cell systems [Madin-Darby canine kidney type II (MDCKII) stably transfected with human BCRP (MDCKII/BCRP) or human P-gp (MDCKII/P-gp)]. The transepithelial flux of 3 H-Digoxin and 3 H-Estrone sulfate, prototypic substrates of P-gp, and BCRP, respectively, across Caco-2 cell monolayers, MDCKII/BCRP, and MDCKII/P-gp cells were determined. The results demonstrate that black ginger extract (10 μg/ml) significantly increases 3 H-Digoxin and 3 H-Estrone sulfate transport from the apical to basolateral side while decreasing transport from the basolateral to apical side of Caco-2 cells and MDCKII cell overexpression of BCRP or P-gp. The effect of the extract on 3 H-Digoxin and 3 H-Estrone sulfate transport was related to a decrease in efflux ratio. Likewise, DMF (5 μM) significantly increased 3 H-Digoxin and 3 H-Estrone sulfate absorption with a decreased efflux ratio compared to the control. Interestingly, the extract also significantly increased absorption of paclitaxel, an anti-cancer drug, which has poor oral absorption. Taken together, co-administration of drugs as substrates of BCRP and P-gp, with the black ginger extract containing DMF, might alter the pharmacokinetic profiles of the medicine.