Rimac Hrvoje, Dufour Claire, Debeljak Željko, Zorc Branka, Bojić Mirza
Department of Medicinal Chemistry, University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10000 Zagreb, Croatia.
UMR408 SQPOV, Safety and Quality of Plant Products, INRA, Avignon University, 228 Route de l'Aérodrome, 84000 Avignon, France.
Molecules. 2017 Jul 11;22(7):1153. doi: 10.3390/molecules22071153.
Human serum albumin (HSA) binds a variety of xenobiotics, including flavonoids and warfarin. The binding of another ligand to the IIA binding site on HSA can cause warfarin displacement and potentially the elevation of its free concentration in blood. Studies dealing with flavonoid-induced warfarin displacement from HSA provided controversial results: estimated risk of displacement ranged from none to serious. To resolve these controversies, in vitro study of simultaneous binding of warfarin and eight different flavonoid aglycons and glycosides to HSA was carried out by fluorescence spectroscopy as well as molecular docking. Results show that warfarin and flavonoids do not share the same binding region in binding to HSA. Interactions were only observed at high warfarin concentrations not attainable under recommended dosing regimes. Docking experiments show that flavonoid aglycons and glycosides do not bind at warfarin high affinity sites, but rather to different regions within the IIA HSA subdomain. Thus, the risk of clinically significant warfarin-flavonoid interaction in binding to HSA should be regarded as negligible.
人血清白蛋白（HSA）可结合多种外源性物质，包括黄酮类化合物和华法林。另一种配体与HSA上的IIA结合位点结合会导致华法林被置换，进而可能使其在血液中的游离浓度升高。关于黄酮类化合物诱导华法林从HSA上被置换的研究结果存在争议：估计的置换风险范围从无到严重。为了解决这些争议，通过荧光光谱法以及分子对接技术，对华法林与八种不同黄酮苷元和糖苷同时与HSA结合进行了体外研究。结果表明，华法林和黄酮类化合物在与HSA结合时并不共享相同的结合区域。仅在推荐给药方案下无法达到的高华法林浓度时才观察到相互作用。对接实验表明，黄酮苷元和糖苷并不结合在华法林的高亲和力位点，而是结合在IIA HSA亚结构域内的不同区域。因此，临床上华法林与黄酮类化合物在与HSA结合时发生显著相互作用的风险应被视为可忽略不计。
