Hatano T, Yasuhara T, Yoshihara R, Agata I, Noro T, Okuda T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Chem Pharm Bull (Tokyo). 1990 May;38(5):1224-9. doi: 10.1248/cpb.38.1224.
The inhibitory effects of hydrolyzable tannins, condensed tannins and related polyphenols on the activity of xanthine oxidase (XOD), catalyzing uric acid formation from xanthine, were investigated. Marked differences in the strength of the inhibition were observed. Some of the differences among the monomeric hydrolyzable tannins were due to their molecular weights, reflecting the number of phenolic hydroxyl groups in the molecule. However, the inhibitory activity of several oligomeric hydrolyzable tannins seemed particularly low in spite of their large molecular size. It was also observed that differences in location of acyl groups on the carbohydrate cores caused differences in the inhibitory activity among monomeric and oligomeric hydrolyzable tannins. A caffeic acid derivative (caffeetannin), 3,5-di-O-caffeoylquinic acid (24), also inhibited this enzyme. Galloylation and the degree of polymerization in proanthocyanidins were also shown to affect remarkably the strength of the inhibition. Among the compounds tested in the present study, valoneic acid dilactone (29), isolated from Mallotus japonicus, inhibited the enzyme most effectively. A kinetic study showed that this dilactone inhibited XOD non-competitively. Comparison of the inhibitory effect on XOD, with the binding activity to hemoglobin, for each tannin, suggests that their inhibition of XOD is not based on non-specific binding to the protein. Similar comparison of the inhibitory effect on XOD with the inhibitory effect on the generation of superoxide anion radical (O2-.) from the hypoxanthine-XOD system revealed that the inhibition of O2-. generation by tannins is due to their radical-scavenging activity, and not due to their inhibitory activity upon the enzyme.
研究了可水解单宁、缩合单宁及相关多酚对黄嘌呤氧化酶（XOD）活性的抑制作用，该酶催化黄嘌呤生成尿酸。观察到抑制强度存在显著差异。单体可水解单宁之间的一些差异归因于它们的分子量，这反映了分子中酚羟基的数量。然而，几种低聚可水解单宁尽管分子量大，但其抑制活性似乎特别低。还观察到碳水化合物核心上酰基位置的差异导致单体和低聚可水解单宁之间抑制活性的差异。一种咖啡酸衍生物（咖啡单宁），3,5-二-O-咖啡酰奎尼酸（24），也抑制这种酶。原花青素中的没食子酰化和聚合度也被证明对抑制强度有显著影响。在本研究中测试的化合物中，从日本野桐中分离出的戊酮酸双内酯（29）对该酶的抑制作用最有效。动力学研究表明，这种双内酯对XOD的抑制是非竞争性的。比较每种单宁对XOD的抑制作用与对血红蛋白的结合活性，表明它们对XOD的抑制不是基于与蛋白质的非特异性结合。将对XOD的抑制作用与对次黄嘌呤-XOD系统中超氧阴离子自由基（O2-·）生成的抑制作用进行类似比较，发现单宁对O2-·生成的抑制是由于它们的自由基清除活性，而不是由于它们对酶的抑制活性。
