Interactions between Oroxylin A with the solute carrier transporters and ATP-binding cassette transporters: Drug transporters profile for this flavonoid.

Abstract Oroxylin A is a flavonoid monomer extracted from Scutellaria baicalensis Georgi with neuroprotective, anti-tumor activity and many other biological functions. However, the interaction between Oroxylin A and the drug transporters has not been clearly reported. The purpose of this study is to investigate the interaction between Oroxylin A and the solute carrier transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, and MATE2K), and ATP-binding cassette transporters (BCRP, MDR1). The HEK293 cell lines (HEK293-OATP1B1, HEK293-OATP1B3, HEK293-OAT1, HEK293-OAT3, HEK293-OCT2, HEK293-MATE1, and HEK293-MATE2K) that stably expressing previous listed human-derived transporters were employed to evaluate the solute carrier transporters. Vesicles expressing human BCRP and MDR1 transporters was employed to research ATP-binding cassette transporters. Our work suggested that Oroxylin A was a substrate of OATP1B1, OATP1B3, but not a substrate of the other transporters in the concentration range of our study. Oroxylin A shows concentration-dependent inhibition of OATP1B1, OAT1, OAT3 and BCRP transportation with the half-inhibitory concentration (IC50) of 7.03, 0.961, 0.112 μM, and 0.477 μM, respectively. No inhibitory effects on the transport activities of other transporters were observed for Oroxylin A. Drug transporters profile of Oroxylin A was first confirmed by our work, which provides important information for its pharmacokinetics, pharmacodynamics, and drug-drug interactions studies.