title: Spectroscopic and molecular docking studies of the in vitro interaction between puerarin and cytochrome P450.
abstract: Puerarin, an isoflavone glycoside extracted from Pueraria plants, has various medical functions. Cytochrome P450s (CYPs) are crucial phase I metabolizing enzymes, which have been spotlighted for their effects on drug metabolism. The interaction between puerarin and CYPs (CYP1A2 and CYP2D6) was investigated by fluorescence, UV-Vis and circular dichroism spectroscopies, as well as molecular docking, to explore the underlying mechanism under simulated physiological conditions. The molecular docking results indicated that puerarin interacted with CYPs mainly by hydrophobic force and hydrogen bonding. The fluorescences of CYPs were quenched statically. Binding constants (Ka) and number of binding sites (n) at different temperatures were calculated, with the results being consistent with those of molecular docking. At the same temperature, puerarin bound to CYP1A2 more weakly than it did to CYP2D6. UV-Vis and circular dichroism spectroscopies confirmed the micro-environmental and conformational changes of CYP1A2 and CYP2D6. The findings provide reliable evidence for clarifying the structures and functions of CYPs.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Avenue No. 138, Nanjing 210023, China. shao.jiangjuan.cbfp@gmail.com.
authors.forename: Jiangjuan
authors.initials: J
authors.lastname: Shao
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Avenue No. 138, Nanjing 210023, China. chenjw695@126.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Chen
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Avenue No. 138, Nanjing 210023, China. ttli734493813@163.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Xianlin Avenue No. 138, Nanjing 210023, China. xlee_zhao@163.com.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhao
mesh_terms: D001665:Binding Sites; D019388:Cytochrome P-450 CYP1A2 / Q000737:chemistry*; D019389:Cytochrome P-450 CYP2D6 / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007529:Isoflavones / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014665:Vasodilator Agents / Q000737:chemistry*
chemical_list: D007529:Isoflavones; D014665:Vasodilator Agents; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; C033607:puerarin
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