A Brief Review of Natural Products with Urate Transporter 1 Inhibition for the Treatment of Hyperuricemia.

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.