Honda Sari, Fukuyama Yuya, Nishiwaki Hisashi, Masuda Akiko, Masuda Toshiya
Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan.
Graduate School of Agriculture, Ehime University, Matsuyama 790-8566, Japan.
Free Radic Biol Med. 2017 May;106:228-235. doi: 10.1016/j.freeradbiomed.2017.02.037. Epub 2017 Feb 20.
In this study, the mechanism of the xanthine oxidase (XO) inhibitory activity of pyrogallol, the main inhibitor found in roasted coffee, was investigated. Pyrogallol was unstable and readily converted to purpurogallin in a pH 7.4 solution, a physiological model of human body fluids. The XO inhibitory activity of the produced purpurogallin was higher than that of pyrogallol, as evidenced by comparing their IC values (0.2µmolL for purpurogallin, 1.6µmolL for pyrogallol). The XO activity of pyrogallol was enhanced by pre-incubation in pH 7.4 solution. Although the initial XO inhibitory activity of 4-methylpyrogallol was weak (IC 33.3µmolL), its XO inhibitory activity was also enhanced by pre-incubation in the pH 7.4 solution. In contrast, 5-methylpyrogallol, which could not be transformed into corresponding purpurogallin derivatives, did not show XO inhibitory activity before or after incubation in pH 7.4 solution. Molecular docking simulations clarified that purpurogallins have stronger affinities for XO than corresponding pyrogallols. These results revealed that the potent XO inhibitory activity seemingly observed in pyrogallol is actually derived from its chemical conversion, under alkaline conditions, into purpurogallin.
在本研究中，对烘焙咖啡中主要的抑制剂连苯三酚的黄嘌呤氧化酶（XO）抑制活性机制进行了研究。连苯三酚不稳定，在pH 7.4溶液（一种人体体液的生理模型）中容易转化为红紫素。通过比较它们的IC值（红紫素为0.2µmol/L，连苯三酚为1.6µmol/L）可以证明，所产生的红紫素的XO抑制活性高于连苯三酚。连苯三酚在pH 7.4溶液中预孵育后其XO活性增强。尽管4-甲基连苯三酚最初的XO抑制活性较弱（IC为33.3µmol/L），但其XO抑制活性在pH 7.4溶液中预孵育后也有所增强。相比之下，不能转化为相应红紫素衍生物的5-甲基连苯三酚在pH 7.4溶液中孵育前后均未表现出XO抑制活性。分子对接模拟表明，红紫素对XO的亲和力比相应的连苯三酚更强。这些结果表明，连苯三酚中看似观察到的强大XO抑制活性实际上源于其在碱性条件下化学转化为红紫素。
