title: Reductive metabolism of oxymatrine is catalyzed by microsomal CYP3A4.
abstract: Oxymatrine (OMT) is a pharmacologically active primary quinolizidine alkaloid with various beneficial and toxic effects. It is confirmed that, after oral administration, OMT could be transformed to the more toxic metabolite matrine (MT), and this process may be through the reduction reaction, but the study on the characteristics of this transformation is limited. The aim of this study was to investigate the characteristics of this transformation of OMT in the human liver microsomes (HLMs) and human intestinal microsomes (HIMs) and the cytochrome P450 (CYP) isoforms involved in this transformation. The current studies demonstrated that OMT could be metabolized to MT rapidly in HLMs and HIMs and CYP3A4 greatly contributed to this transformation. All HLMs, HIMs, and CYP3A4 isoform mediated reduction reaction followed typical biphasic kinetic model, and Km, Vmax, and CL were significant higher in HLMs than those in HIMs. Importantly, different oxygen contents could significantly affect the metabolism of OMT, and with the oxygen content decreased, the formation of metabolite was increased, suggesting this transformation was very likely a reduction reaction. Results of this in vitro study elucidated the metabolic pathways and characteristics of metabolism of OMT to MT and would provide a theoretical basis and guidance for the safe application of OMT.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China ; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Wenqin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China ; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Lingna
authors.initials: L
authors.lastname: Dong
authors.affiliation: International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Luo
authors.affiliation: International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China ; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.affiliation: International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China ; International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000378:metabolism*; D000998:Antiviral Agents / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010100:Oxygen; D011807:Quinolizines / Q000378:metabolism*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; D007527:Isoenzymes; D011807:Quinolizines; C037573:oxymatrine; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010100:Oxygen; D000093842:Matrines
keywords: CYP3A4; matrine; metabolism; microsomes; oxymatrine; reduction reaction