高尿酸血症(HUA)是严重危害人体健康的代谢性疾病，但目前的药物主要针对尿酸转运蛋白治疗疗效不佳。前期研究发现牛尾菜以多成分基于体内过程协同而显著抗HUA，且与尿酸转运关键蛋白URAT1、GLUT9、ABCG2及上游炎症小体NLRP3相关。本项目拟以牛尾菜药材降尿酸谱效关系结合牛尾菜总提取物体内多组分药动/效动进行关联分析，综合应用HPLC-MSn等解析降尿酸的药效成分，阐明牛尾菜抗HUA药效物质基础；继之以分子对接结合分子生物学实验揭示各药效物质作用于NLRP3/Caspase-1/PDZK1轴及下游URAT1、GLUT9、ABCG2中的哪个关键环节；再从药动学协同、药效学协同及协同对靶点结合构象改变等三方面综合阐释药效成分间协同机制。为科学利用牛尾菜药材及开发新型抗HUA药物奠定基础；也为更多能基于NLRP3/Caspase-1/PDZK1轴抗HUA的中药药效物质及机制研究提供参考。

Hyperuricemia(HUA) is a kind of metabolic disease seriously harmful to human health. While the current efficiency of drug therapy targeting on uric acid transporters is not satisfactory. Our previous study found that Smilax riparia could against HUA through the synergy of multi-component in vivo, which is related to the key proteins in uric acid transportation including URAT1, GLUT9 and ABCG2, as well as upstream inflammasome, NLRP3. Therefore, our project illustrated the material foundation of Smilax riparia’s anti-hyperuricemia effect through uric acid-lowering spectrum-effect relationship, pharmacokinetic-pharmacodynamic association analysis of Smilax riparia’s total extract and the analysis of active ingredients using HPLC-MSn, et al. Furthermore, to illustrate the targets that pharmacodynamic materials acting on in NLRP3/Caspase-1/PDZK1 axis and downstream uric acid transporters, URAT1, GLUT9 and ABCG2, we used molecular docking combining with biology experiments. In addition, we illustrated the synergy mechanism from three aspects, the pharmacokinetic synergy, the pharmacodynamic synergy and targets’ conformational changes due to the synergy effect. Our project laid the foundation for the scientific utilization of Smilax riparia and the development of new anti-hyperuricemia drugs, meanwhile, providing references for other studies on anti-hyperuricemia pharmacodynamic material and mechanism based on NLRP3/Caspase-1/PDZK1 axis.