title: In vitro metabolism and disposition of honokiol in rat and human livers.
abstract: The biotransformation of honokiol, a major constituent of the bark of Magnolia officinalis, was investigated in rat and human livers. When isolated, rat livers were perfused with 10 µM honokiol and two metabolites, namely hydroxylated honokiol conjugated with glucuronic and sulfuric acid (M1) and honokiol monoglucuronide (M2), were quantified in bile and perfusate by high-performance liquid chromatography. The hepatic extraction ratio and clearance of honokiol was very high in rat liver (E: 0.99 ± 0.01 and 35.8 ± 0.04 mL/min, respectively) leading to very low bioavailability (F = 0.007 ± 0.001). M2 formation was also highly efficient in human liver microsomes [V(max) /K(m) = 78.1 ± 6.73 µL/(min mg)], which appeared to be catalyzed mainly by UDP-glucuronosyltransferases 1A1, A3, 1A8, and 1A10, indicating hepatic and extrahepatic glucuronidation. Monosulfation of honokiol to the minor metabolite honokiol monosulfate [V(max) /K(m) = 27.9 ± 4.33 µL/(min mg)] by human liver cytosol was less pronounced and is mediated by sulfotransferases 1A1* 1, 1A1* 2, 1A2, 1A3, 1B1, and 1E1. P450-mediated oxidation of honokiol by liver microsomes, however, was below detection limit. In summary, this study established that glucuronidation and sulfation are the main metabolic pathways for honokiol in rat and human liver, suggesting their major contribution to clearance in vivo.
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Böhmdorfer
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Maier-Salamon
authors.affiliation: Department of Pharmacology and Toxicology, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Taferner
authors.affiliation: Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Reznicek
authors.affiliation: Institute of Pathophysiology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Theresia
authors.initials: T
authors.lastname: Thalhammer
authors.affiliation: Department of Pharmacology and Toxicology, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Karl-Franzens-University Graz, A-8010 Graz, Austria.
authors.forename: Antje
authors.initials: A
authors.lastname: Hüfner
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University Graz, A-8010 Graz, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schühly
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria. Electronic address: walter.jaeger@univie.ac.at.
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D001713:Biphenyl Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D020723:Glucuronic Acid / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007313:Insecta; D017705:Lignans / Q000378:metabolism / Q000493:pharmacokinetics*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D031566:Magnolia / Q000737:chemistry; D008297:Male; D050216:Metabolic Detoxication, Phase I; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013464:Sulfuric Acids / Q000378:metabolism; D014018:Tissue Distribution; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D020723:Glucuronic Acid; D017705:Lignans; D013464:Sulfuric Acids; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C033158:sulfuric acid