Identification of cytochrome P450 (CYP) isoforms involved in the metabolism of corynoline, and assessment of its herb-drug interactions

Phytotherapy Research : PTR
Zhong-Ze FangLing Yang

Abstract

Corynoline, an isoquinoline alkaloid isolated from the genus Corydalis, has been demonstrated to show multiple pharmacological effects including inhibition of acetylcholinesterase, inhibition of cell adhesion, fungitoxic and cytotoxic activity. The present study focused on its metabolism and metabolism-based herb-drug interactions. After corynoline was incubated with human liver microsomes (HLMs) in the presence of NADPH, two metabolites (M-1 and M-2) were formed. Chemical inhibition experiments and assays with recombinant CYP isoforms showed that CYP2C9 was mainly involved in the formation of M-1 and CYP3A4 mainly catalysed the production of M-2. Among seven major CYP isoforms tested, corynoline showed strong inhibitory effects on the activities of CYP3A4 and CYP2C9, with an IC(50) of 3.3 ± 0.9 µm and 31.5 ± 0.5 µm, respectively. Kinetic analysis showed that inhibition of CYP3A4 by corynoline was best fit to a noncompetitive manner with K(i) of 3.2 µm, while inhibition of CYP2C9 by corynoline was best fit to a competitive manner with K(i) of 6.3 µm. Additionally, corynoline exhibited time-dependent inhibition (TDI) toward CYP3A4. The inactivation kinetic parameters (K(I) and k(inact) ) were calculated to be 6.8 µm and 0.07 min...Continue Reading

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Citations

Apr 9, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Fahad I Al-JenoobiSaleh A Al-Suwayeh
Aug 21, 2013·BioMed Research International·F I Al-JenoobiMohd Raish
Jan 4, 2019·The Journal of Membrane Biology·Meishan ZhangShuqiang Liu
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Aug 12, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xu MaoJiang Zheng
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May 26, 2011·Expert Opinion on Drug Metabolism & Toxicology·Zhong-Ze FangLing Yang

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