Abstract

Magnolin, a bioactive lignan separated from Flos Magnoliae, possesses anti-inflammatory, anticancer, antioxidant, and vasodilator effects. This study compared the metabolic profiles of magnolin in human and rat hepatocytes using liquid chro- matography-high resolution mass spectrometry. The hepatic extraction ratio of magnolin in human and rat hepatocytes were 0.27 and 0.14, respectively, suggesting that it undergoes a low-to-moderate degree of hepatic metabolism. During metabolism in human hepatocytes, magnolin generated 8 phase 1 metabolites, including O-desmethylmagnolin (M1-M4), hydroxymagnolin (M5), di-O-desmethylmagnolin (M6 and M7), and hydroxy-O-desmethylmagnolin (M8), and 11 phase 2 metabolites, including glucuronides of M1-M4 (M9-M12) and M7 (M15), sulfates of M1, M2, M6, and M7 (M13, M14, and M16-M18), and M6 disulfate (M19). However, 6 phase 1 metabolites (M1-M5 and M8) and 6 phase 2 metabolites (M9-M14) were formed after incubation of magnolin with rat hepatocytes. These findings help to predict the pharmacokinetics and metabolism of magnolin in humans.