title: In vitro metabolism of 20(R)-25-methoxyl-dammarane-3, 12, 20-triol from Panax notoginseng in human, monkey, dog, rat, and mouse liver microsomes.
abstract: The present study characterized in vitro metabolites of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol (20(R)-25-OCH3-PPD) in mouse, rat, dog, monkey and human liver microsomes. 20(R)-25-OCH3-PPD was incubated with liver microsomes in the presence of NADPH. The reaction mixtures and the metabolites were identified on the basis of their mass profiles using LC-Q/TOF and were quantified using triple quadrupole instrument by multiple reaction monitoring. A total of 7 metabolites (M1-M7) of the phase I metabolites were detected in all species. 25(R)-OCH3-PPD was metabolized by hydroxylation, dehydrogenation, and O-demethylation. Enzyme kinetic of 20(R)-25-OCH3-PPD metabolism was evaluated in rat and human hepatic microsomes. Incubations studies with selective chemical inhibitors demonstrated that the metabolism of 20(R)-25-OCH3-PPD was primarily mediated by CYP3A4. We conclude that 20(R)-25-OCH3-PPD was metabolized extensively in mammalian species of mouse, rat, dog, monkey, and human. CYP3A4-catalyzed oxygenation metabolism played an important role in the disposition of 25(R)-OCH3-PPD, especially at the C-20 hydroxyl group.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
authors.forename: Baoshan
authors.initials: B
authors.lastname: Sun
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Guo
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Shi
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning, China; Key Laboratory of Research and Design of "Drug Targets Based on the Ministry of Education", Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D053723:Panax notoginseng / Q000737:chemistry*; D051381:Rats; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism*; D000097669:Dammaranes
chemical_list: D014315:Triterpenes; D000097669:Dammaranes
references.citation: Lung Cancer. 2009 Sep;65(3):306-11
references.pmid: 19131140
references.citation: Xenobiotica. 2009 Jun;39(6):457-64
references.pmid: 19480551
references.citation: PLoS One. 2012;7(7):e41586
references.pmid: 22911819
references.citation: Altern Med Rev. 2004 Sep;9(3):259-74
references.pmid: 15387718
references.citation: PLoS One. 2008 Jul 16;3(7):e2697
references.pmid: 18628990
references.citation: Biochem Pharmacol. 1999 Dec 1;58(11):1685-93
references.pmid: 10571242
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1417-24
references.pmid: 19632285
references.citation: Biochim Biophys Acta. 2013 Aug;1830(8):4148-59
references.pmid: 23583729
references.citation: Drug Metab Dispos. 2012 Oct;40(10):2041-53
references.pmid: 22829543
references.citation: Med Chem. 2007 Jan;3(1):51-60
references.pmid: 17266624
references.citation: Xenobiotica. 2013 Oct;43(10):868-74
references.pmid: 23631760
references.citation: Cancer Lett. 2009 Jun 18;278(2):241-248
references.pmid: 19203832
references.citation: Cancer Lett. 2010 Mar 1;289(1):99-110
references.pmid: 19765891
references.citation: Bioorg Med Chem Lett. 2011 Feb 1;21(3):1027-31
references.pmid: 21216145
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 15;858(1-2):65-70
references.pmid: 17825630
references.citation: Br J Cancer. 2008 Feb 26;98(4):792-802
references.pmid: 18253123