Qualitative and quantitative analysis of drug interactions: Fritillary mediating the transport of alkaloids in caco-2 cells by p-glycoprotein

Abstract

Ultra performance liquid chromatographic-electrospray ionization-mass spectrometry(UPLC-ESI-MS) was used to investigate the potential interaction between selected ingredients of Aconitum and fritillary. The efflux ratios of 14-benzoylmesaconine(BM), 14-benzoylaconine(BC), 14-benzoylhypaconine(BH), mesaconitine(MA), aconitine( AC) and hypaconitine(HA) was 11.16, 12.53, 11.69, 12.8, 11.03 and 6.15, respectively, and the secretion of them was inhibited by Verapamil, which means they are the substrates of permeability-glycoprotein(P-gp). The transport of Aconitum alkaloids extract through a Caco-2 cell monolayer was determined in the absence and presence of fritillary extract. And the fritillary extract increased the absorption of Aconitum alkaloids. Peimine(PE) and peiminine( PEN) in fritillary increased the absorption of pure Aconitum alkaloids. The transport of digoxin was respectively enhanced by PE and PEN, which means they are the inhibitors of P-gp. PEN showed more effective inhibition than PE at the same concentration. The in vitro data suggest that the compounds such as fritillary present in alkaloids were able to inhibit the P-gp activity and lead modifying the transport of alkaloids.

Keywords

Aconitum alkaloids / Fritillary / Caco-2 cell / P-Glycoprotein(P-gp) / Ultra performance liquid chromatographic-electrospray ionization-mass spectrometry(UPLC-ESI-MS)

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