The College of Chemistry, Changchun Normal University, Changchun, China.
Luminescence. 2021 Sep;36(6):1412-1421. doi: 10.1002/bio.4065. Epub 2021 Jun 2.
Astilbin, isoastilbin and neoastilbin are the three flavonoid isomers prevalent in Rhizoma Smilax glabra. The interactions between human cytochrome P450 2D6 (CYP2D6) and the three isomers were investigated by multiple spectroscopic coupled with molecular docking. As a result, the fluorescence intensity of CYP2D6 was quenched statically by the three isomers. Meanwhile, astilbin had the strongest binding ability to CYP2D6, followed by isoastilbin and neoastilbin under the identical temperature. Synchronous fluorescence, three-dimensional fluorescence, ultraviolet-visible spectroscopy, circular dichroism and Fourier-transform infrared spectra confirmed that the conformation and micro-environment of CYP2D6 protein were changed after binding with the three isomers. As suggested from molecular docking, the three isomers had strong binding affinity to CYP2D6 via the bonding of hydrogen and van der Waals forces, and the results were in agreement with the fluorescence results. The findings here suggested that astilbin, isoastilbin and neoastilbin may cause the herb-drug interactions for their inhibition of CYP2D6 activity.
紫云英苷、异紫云英苷和新紫云英苷是菝葜中三种常见的黄酮类同分异构体。本研究采用多种光谱学方法结合分子对接技术，研究了三种同分异构体与人细胞色素 P450 2D6（CYP2D6）之间的相互作用。结果表明，三种同分异构体均能使 CYP2D6 的荧光强度发生静态猝灭。在相同温度下，紫云英苷与 CYP2D6 的结合能力最强，其次是异紫云英苷和新紫云英苷。同步荧光、三维荧光、紫外-可见光谱、圆二色光谱和傅里叶变换红外光谱证实，三种同分异构体与 CYP2D6 结合后，CYP2D6 蛋白的构象和微环境发生了变化。分子对接结果表明，三种同分异构体通过氢键和范德华力与 CYP2D6 具有较强的结合亲和力，这与荧光实验结果一致。综上所述，紫云英苷、异紫云英苷和新紫云英苷可能通过抑制 CYP2D6 活性而引起药物-药物相互作用。
