Pharmacokinetic study of the interaction between luteolin and magnoflorine in rats

Both luteolin and magnoflorine have been reported to regulate the development of breast cancer, which makes them easier to co-administrate. Luteolin was co-administrated with magnoflorine to evaluate their potential interaction. The pharmacokinetic study was performed on male Sprague-Dawley rats randomly grouped as the single administration of luteolin and the co-administration of luteolin and magnoflorine with six rats of each. CaCO-2 cell transwell assay was employed for transport evaluation, and the metabolic stability of luteolin and CYP3A activity were assessed in rat liver microsomes. The effect of luteolin on MDA-MB-231 cells was assessed with CCK8 assay. Magnoflorine significantly changed the pharmacokinetic profile of luteolin with increased area under the curve (AUC), prolonged t_1/2 , and reduced clearance rate. Magnoflorine also suppressed the efflux ratio and improved the in vitro metabolic stability of luteolin. Magnoflorine also enhanced the inhibitory effect of luteolin on MDA-MB-231 cells. Magnoflorine significantly inhibited CYP3A activity with the IC₅₀ of 18.99 μM. Magnoflorine prolonged the system exposure, enhanced the metabolic stability, and enhanced the anti-tumor effect of luteolin through inactivating CYP3A.