School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.
School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.
Food Chem. 2019 Jan 30;272:453-461. doi: 10.1016/j.foodchem.2018.08.057. Epub 2018 Aug 14.
This study follows recent attempts to discover natural xanthine oxidase (XO) inhibitors from foods, focusing herein on under-researched fish proteins. The anti-hyperuricemic function of tuna flesh hydrolysate (TPH) produced using Alcalase 2.4L was confirmed in potassium oxonate-induced hyperuricemic rats. TPH was separated using 80 wt% aqueous ethanol. The ethanol-soluble fraction (ESF) abundant in small peptides (<1000 Da) afforded the highest XO inhibition. Separation of ESF by Sephadex G-15 and UPLC/MS/MS revealed 13 di-/tri-peptides (12 are newly identified XO inhibitors). Their XO inhibitory activities were assessed using corresponding synthetic peptides via an improved HPLC method. Results indicate that Phe-containing peptides were more potent XO inhibitors than Trp-containing peptides, with Phe-His having the highest XO inhibitory activity (IC = 25.7 mM). Molecular docking studies revealed the importance of two hydrogen bonds and one π-π stacking interaction with Phe-914 in XO for XO-peptide inhibitor binding. Phe-containing di-/tri-peptides could be potent XO inhibitors against hyperuricemia.
本研究旨在从食物中寻找天然黄嘌呤氧化酶 (XO) 抑制剂，特别关注研究较少的鱼类蛋白质。使用 Alcalase 2.4L 生产的金枪鱼肌肉水解物 (TPH) 的抗高尿酸血症功能在黄嘌呤氧化酶诱导的高尿酸血症大鼠中得到了证实。TPH 用 80wt%的水乙醇分离。富含小肽 (<1000Da) 的乙醇可溶部分 (ESF) 提供了最高的 XO 抑制活性。通过 Sephadex G-15 和 UPLC/MS/MS 分离 ESF，发现了 13 种二肽/三肽 (其中 12 种是新鉴定的 XO 抑制剂)。通过改进的 HPLC 方法，使用相应的合成肽评估它们对 XO 的抑制活性。结果表明，含苯丙氨酸的肽比含色氨酸的肽具有更高的 XO 抑制活性，其中苯丙氨酸-组氨酸的 XO 抑制活性最高 (IC = 25.7mM)。分子对接研究表明，与 XO 中 Phe-914 的两个氢键和一个 π-π 堆积相互作用对于 XO-肽抑制剂结合非常重要。含苯丙氨酸的二肽/三肽可能是抗高尿酸血症的有效 XO 抑制剂。
