Effect of Soy Sauce on Serum Uric Acid Levels in Hyperuricemic Rats and Identification of Flazin as a Potent Xanthine Oxidase Inhibitor
Effect of Soy Sauce on Serum Uric Acid Levels in Hyperuricemic Rats and Identification of Flazin as a Potent Xanthine Oxidase Inhibitor
复制标题
酱油对高尿酸血症大鼠血清尿酸水平的影响及黄嘌呤氧化酶强效抑制剂 Flazin 的鉴定
DOI：
10.1021/acs.jafc.6b01094
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发表时间：
2016-06-15
影响因子：
6.1
通讯作者：
Wang, Yong
中科院分区：
文献类型：
--
作者：
Li, Huipin;Zhao, Mouming;Wang, Yong
本文首次报道酱料能有效降低高尿酸血症大鼠血清尿酸水平和黄嘌呤氧化酶（XOD）活性。酱料依次分配成乙酸乙酯和水馏分。对抑制XOD作用较强的乙酸乙酯部分进行了进一步纯化。在此基础上，采用黄嘌呤氧化酶抑制活性导向纯化技术，从其粗提物中分离得到9个化合物，包括肉桂酸3，4-二羟基乙酯、对苯二甲酸二异丁酯、哈曼、大豆苷元、黄酮、邻苯二酚、胸腺嘧啶、染料木素和尿嘧啶。首次从酱料中分离出肉桂酸3，4-二羟基乙酯和对苯二甲酸二异丁酯。在C-1位具有羟甲基呋喃酮基团和在C-3位具有羧基的Flazin显示出最强的XOI活性（IC 50 = 0.51 +/- 0.05 mM）。荧光猝灭和分子对接实验表明，flazin可以进入XOD的催化中心，与Lys 1045、Gln 1194和Arg 912主要通过疏水力和氢键作用。Flazin、邻苯二酚和染料木素不仅是有效的XOD抑制剂，而且具有一定的抗氧化活性。根据ADME（吸收、分布、代谢和排泄）的计算机模拟，黄酮苷在体内具有良好的口服生物利用度。
This is the first report on the ability of soy sauce to effectively reduce the serum uric acid levels and xanthine oxidase (XOD) activities of hyperuricemic rats. Soy sauce was-partitioned sequentially into ethyl acetate and water fractions. The ethyl acetate fraction with strong XOD inhibition effect was purified further. On, the basis of xanthine oxidase inhibitory (XOI) activity-guided purification, nine compounds including 3,4-dihydroxy ethyl cinnamate, diisobutyl terephthalate, harman, daidzein, flazin, catechol, thymine, genistein, and uracil were obtained. It was the first time that 3,4-dihydroxy ethyl cinnamate and diisobutyl terephthalate had been identified from soy sauce. Flazin with hydroxymethyl furan ketone group at C-1 and carboxyl at C-3 exhibited the strongest XOI activity (IC50 = 0.51 +/- 0.05 mM). According to fluorescence quenching and molecular docking experiments, flazin could enter into the catalytic center of XOD to interact with Lys1045, Gln1194, and Arg912 mainly by hydrophobic forces and hydrogen bonds. Flazin, catechol, and genistein not only were potent XOD inhibitors but also held certain antioxidant activities. According to ADME (absorption, distribution, metabolism, and excretion) simulation in silico, flazin had good oral bioavailability in vivo.