Yuan Qianghua, Cheng Yuan, Sheng Rong, Yuan Yan, Hu Mei
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610041, China.
School of Medical and Life Sciences/Reproductive & Women-Children Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610041, China.
Evid Based Complement Alternat Med. 2022 Oct 28;2022:5419890. doi: 10.1155/2022/5419890. eCollection 2022.
Hyperuricemia is a common disease caused by a high level of uric acid. Urate transporter 1 (URAT1) is an important protein and mediates approximately 90% of uric acid reabsorption. Therefore, the URAT1 inhibitor is a class of uricosuric medicines widely used in the clinic for the treatment of hyperuricemia. To find the new medicine with stronger URAT1 inhibition and lower toxicity, researchers have been exploring natural products. This study systematically summarizes the natural products with URAT1 inhibition. The results show that many natural products are potential URAT1 inhibitors, such as flavonoids, terpenoids, alkaloids, coumarins, stilbenes, and steroids, among which flavonoids are the most promising source of URAT1 inhibitors. It is worth noting that most studies have focused on finding natural products with inhibition of URAT1 and have not explored their activities and mechanisms toward URAT1. By reviewing the few existing studies of the structure-activity relationship and analyzing common features of natural products with URAT1 inhibition, we speculate that the rigid ring structure and negative charge may be the keys for natural products to produce URAT1 inhibition. In conclusion, natural products are potential URAT1 inhibitors, and exploring the mechanism of action and structure-activity relationship will be an important research direction in the future.
高尿酸血症是一种由尿酸水平升高引起的常见疾病。尿酸盐转运蛋白1（URAT1）是一种重要的蛋白质，介导约90%的尿酸重吸收。因此，URAT1抑制剂是一类在临床上广泛用于治疗高尿酸血症的促尿酸排泄药物。为了找到具有更强URAT1抑制作用和更低毒性的新药，研究人员一直在探索天然产物。本研究系统总结了具有URAT1抑制作用的天然产物。结果表明，许多天然产物是潜在的URAT1抑制剂，如黄酮类、萜类、生物碱、香豆素、芪类和甾体类，其中黄酮类是最有前景的URAT1抑制剂来源。值得注意的是，大多数研究都集中在寻找具有URAT1抑制作用的天然产物，而没有探索它们对URAT1的活性和作用机制。通过回顾现有的少数结构-活性关系研究，并分析具有URAT1抑制作用的天然产物的共同特征，我们推测刚性环结构和负电荷可能是天然产物产生URAT1抑制作用的关键。总之，天然产物是潜在的URAT1抑制剂，探索其作用机制和结构-活性关系将是未来的一个重要研究方向。
