ABSORPTION OF HYPACONITINE AND P-GLYCOPROTEIN-MEDIATED DRUG-HYPACONITINE INTERACTIONS BY CACO-2 HUMAN INTESTINAL CELL MONOLAYERS

Abstract

Aconitum species is an essential but toxic herb in Traditional Chinese Medicine (TCM). As a main and characteristic constituent in Aconitum species, hypaconitine (HA) was selected to illustrate the P-glycoprotein-mediated drug-HA interactions using Caco-2 cell monolayers. The HA absorption results revealed that HA was not only an inhibiter but also a substance of P-glycoprotein (P-gp). In TCM theory, it is acknowledged that Aconitum species are incompatible with Bulbus Fritillariae for the increase of the poisoning risk. Peimine and peiminine, which are the active components of Bulbus Fritillariae, increased the bioavailability of HA suggested this effect should be one of the reason to increase the poisoning risk when Bulbus Fritillariae combined with Aconitum species. However, no significant difference in absorption of peimine (PE) or peiminine (PEN) was observed when they combined with HA, respectively. Glycyrrhiza is a famous detoxifying herb in TCM, and the combined use of Glycyrrhiza and Aconitum species is a safe pair in TCM formulations. Liquiritin (LQ) and isoliquiritin (ILQ), which are the active components of Glycyrrhiza, were combined with HA, respectively. The detoxified mechanism of Glycyrrhiza combined with Aconitum species seems less related to the interaction of the absorption.