Abstract
We investigated the inhibitory effect of components in grapefruit juice (GFJ) and orange juice (OJ) on the uptake of vinblastine, a substrate of P-glycoprotein, by Caco-2 cells. Significantly increased uptake of [3H] vinblastine at the steady state by Caco-2 cells was observed in the presence of GFJ and OJ. This suggests that the both juices involve compounds inhibiting P-gp function. We examined the effect of three organic solvent extracts, ethyl acetate, diethyl ether and methylene chrolide, of GO and OJ on the uptake of [3H] vinblastine. The inhibitory effect was shown more in ethyl acetate extracts than the other two extracts, in the both case of GFJ and OJ. Furthermore, the ethyl acetate extracts of GFJ and OJ were fractionated by cosmosil column chromatography with stepwise methanol solution. Inhibitory effect of GFJ on P-gp function was maximun in the fraction eluted with 60% methanol solution, while OJ's was maximun in 70% methanol solution. Each fraction contained different component. Moreover, inhibitory effect of GFJ on CYP3A4 was maximun in the fraction eluted with 80% methanol solution. This study suggested the existence of unknown specific inhibitory compounds in GFJ and OJ for the P-gp, but not for CYP3A4 function.
