Oxypeucedanin Hydrate: A Natural Furanocoumarin as P-Glycoprotein Substrate

Abstract

Oxypeucedanin hydrate is a furanocoumarin widely found in various fruits and vegetables so it may interact with prescribed drugs leading to pharmacokinetic interaction. This study was conducted using in vitro cell culture model to investigate the role of oxypeucedanin hydrate on P-gp function. To evaluate the role of oxypeucedanin hydrate as a P-gp substrate, the bidirectional transport studies of oxypeucedanin hydrate were performed in LLC-PK1 and LLC-GA5-COL300. The corrected efflux ratio of oxypeucedanin hydrate was 3.3 ± 0.7, indicating that it was a P-gp substrate. Calcein AM uptakes performed in comparison between LLC-PK1 and LLC-GA5-COL300 as well as daunorubicin transport across Caco-2 cell monolayer were conducted to examine the inhibition effect of oxypeucedanin hydrate on P-gp. The results exhibited that oxypeucedanin hydrate significantly increased calcein accumulation in LLC-GA5-COL300 in a concentration dependent manner and, moreover, the b-a daunorubicin transport across Caco-2 cell monolayer was decreased from 7 to 5, implying the role of the compound on P-gp inhibition, although the effect was quite minimal. Collectively, the results suggested that oxypeucedanin hydrate could act as P-gp substrate and be likely to inhibit P-gp function.