Lagotis brachystachya Maxim is a herb widely used in traditional Tibetan medicine. Our previous study indicated that total extracts from Lagotis brachystachya could lower uric acid levels. This study aimed to further elucidate the active components (luteolin, luteoloside and apigenin) isolated from Lagotis brachystachya and the underlying mechanism in vitro and in vivo. The results showed that treatment with luteolin and luteoloside reversed the reduction of organic anion transporter 1 (OAT1) levels, while apigenin attenuated the elevation of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) levels in uric acid-treated HK-2 cells, which was consistent with the finding in the kidneys of potassium oxonate (PO)-induced mice. On the other hand, hepatic xanthine oxidase activity was inhibited by the components. In addition, all of these active components improved the morphology of the kidney in hyperuricemic mice. Moreover, molecular docking showed that luteolin, luteoloside and apigenin could bind Toll-like receptor 4 (TLR4) and NLR family pyrin domain containing 3 (NLRP3). Congruently, western blot analysis showed that the components inhibited TLR4/myeloid differentiation primary response 88 (MyD88)/NLRP3 signaling. In conclusion, these results indicated that luteolin, luteoloside and apigenin could attenuate hyperuricemia by decreasing the production and increasing the excretion of uric acid, which were mediated by inhibiting inflammatory signaling pathways.

Lagotis brachystachya Maxim 是一种广泛用于传统藏药的草药。我们之前的研究表明，兔兔总提取物可以降低尿酸水平。本研究旨在进一步阐明从Lagotis brachystachya 中分离的活性成分（木犀草素、木犀草苷和芹菜素）以及体外和体内的潜在机制。结果表明，木犀草素和木犀草苷处理逆转了有机阴离子转运蛋白 1 (OAT1) 水平的降低，而芹菜素减弱了尿酸处理的 HK-2 中尿酸转运蛋白 1 (URAT1) 和葡萄糖转运蛋白 9 (GLUT9) 水平的升高细胞，这与在氧酸钾 (PO) 诱导的小鼠肾脏中的发现一致。另一方面，肝黄嘌呤氧化酶活性受到这些成分的抑制。此外，所有这些活性成分都改善了高尿酸血症小鼠肾脏的形态。此外，分子对接表明木犀草素、木犀草苷和芹菜素可以结合 Toll 样受体 4 (TLR4) 和 NLR 家族 pyrin 结构域 3 (NLRP3)。一致地，蛋白质印迹分析表明，这些成分抑制了 TLR4/骨髓分化初级反应 88 (MyD88)/NLRP3 信号传导。总之，这些结果表明木犀草素、木犀草苷和芹菜素可以通过抑制炎症信号通路介导的降低尿酸的产生和增加排泄来减轻高尿酸血症。