Bencsik Tímea, Balázs Orsolya, Vida Róbert G, Zsidó Balázs Z, Hetényi Csaba, Valentová Kateřina, Poór Miklós
Department of Pharmacognosy, Faculty of Pharmacy, University of Pécs, Pécs, Hungary.
Department of Pharmaceutics and Central Clinical Pharmacy, Faculty of Pharmacy, University of Pécs, Pécs, Hungary.
J Sci Food Agric. 2025 Mar 30;105(5):2765-2776. doi: 10.1002/jsfa.14045. Epub 2024 Nov 28.
Over the past two decades, the global incidence of gout has markedly increased, affecting people worldwide. Considering the side effects of xanthine oxidase (XO) inhibitor drugs (e.g. allopurinol and febuxostat) used in the treatment of hyperuricemia and gout, the potential application of phytochemicals has been widely studied. In addition, XO also takes part in the elimination of certain drugs, including 6-mercaptopurine. In the current explorative study, we aimed to examine the potential effects of tea catechins, resveratrol, silymarin flavonolignans and some of their conjugated metabolites on XO-catalyzed xanthine and 6-mercaptopurine oxidation, applying in vitro assays and modeling studies.
Catechins, resveratrol and resveratrol conjugates exerted no or only weak inhibitory effects on XO. Silybin A, silybin B and isosilybin A were weak, silychristin was a moderate, while 2,3-dehydrosilychristin was a potent inhibitor of the enzyme. Sulfate metabolites of silybin A, silybin B and isosilybin A were considerably stronger inhibitors compared to the parent flavonolignans, and the sulfation of 2,3-dehydrosilychristin slightly increased its inhibitory potency. Silychristin was the sole flavonolignan tested, where sulfate conjugation decreased its inhibitory effect.
2,3-Dehydrosilychristin seems to be a promising candidate for examining its in vivo antihyperuricemic effects, because both the parent compound and its sulfate conjugate are highly potent inhibitors of XO. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
在过去二十年中，全球痛风发病率显著上升，影响着世界各地的人们。鉴于用于治疗高尿酸血症和痛风的黄嘌呤氧化酶（XO）抑制剂药物（如别嘌醇和非布司他）的副作用，植物化学物质的潜在应用已得到广泛研究。此外，XO还参与某些药物的消除，包括6-巯基嘌呤。在当前的探索性研究中，我们旨在通过体外试验和模型研究，考察茶儿茶素、白藜芦醇、水飞蓟素黄酮木脂素及其一些共轭代谢物对XO催化的黄嘌呤和6-巯基嘌呤氧化的潜在影响。
儿茶素、白藜芦醇及其共轭物对XO无抑制作用或仅有微弱抑制作用。水飞蓟宾A、水飞蓟宾B和异水飞蓟宾A的抑制作用较弱，水飞蓟素为中等抑制作用，而2,3-脱氢水飞蓟素是该酶的强效抑制剂。与母体黄酮木脂素相比，水飞蓟宾A、水飞蓟宾B和异水飞蓟宾A的硫酸盐代谢物是更强效的抑制剂，2,3-脱氢水飞蓟素的硫酸化略微增强了其抑制效力。水飞蓟素是唯一 tested 的黄酮木脂素，其硫酸盐共轭作用降低了其抑制效果。
2,3-脱氢水飞蓟素似乎是研究其体内抗高尿酸血症作用的一个有前景的候选物，因为母体化合物及其硫酸盐共轭物都是XO的高效抑制剂。© 2024作者。《食品与农业科学杂志》由约翰·威利父子有限公司代表化学工业协会出版。
