东革阿里改善高尿酸血症的物质基础及作用机制研究

Study on the material basis and mechanism of Eurycoma longifolia in improving hyperuricemia

目的 研究东革阿里改善高尿酸血症的物质基础及作用机制。方法 采用体外酶实验,考察东革阿里不同溶剂提取物对黄嘌呤氧化酶的抑制作用;利用HPLC表征不同溶剂提取物中化学成分的区别;通过网络药理学和分子对接技术预测东革阿里改善高尿酸血症的可能作用机制。结果 东革阿里75%乙醇提取物较水提取物有更好的黄嘌呤氧化酶抑制作用;乙醇提取物中的化学成分以宽缨酮为主,含量为130.4μg·mL-1,而水提取物中宽缨酮含量8μg·mL-1;宽缨酮具有较好的黄嘌呤氧化酶抑制作用,分子对接能量为-5.57 kcal·mol-1;网络药理学发现:活化T细胞核因子5(NFAT5)和胰岛素样生长因子1受体(IGF1R)是宽缨酮、高尿酸血症和炎症三者间的共同靶点,且宽缨酮与两者间对接良好,具有较低的对接能量(-2.88、-4.01 kcal·mol-1)。结论 东革阿里改善高尿酸血症的物质基础与宽缨酮及其类似物有关,其作用机制可能与抑制黄嘌呤氧化酶的活性及与炎症通路的NFAT5和IGF1R两个靶点蛋白有关。

OBJECTIVE To study the material basis and mechanism of Eurycoma longifolia Jack in improving hyperuricemia.METHODS In vitro enzyme experiment was used to investigate the inhibitory effect of different solvent extracts of E.longifolia on xanthine oxidase.The differences of chemical components in different solvent extracts were characterized by HPLC.Network pharmacology and molecular docking methods were used to predict the mechanism of E.longifolia in improving hyperuricemia.RESULTS 75%ethanol extract of E.longifolia(EE)had better inhibitory effect on xanthine oxidase than water extract(WE).The chemical composition of EE was mainly eurycomanone,the content of which was 130.4μg·mL-1,while the content of eurycomanone in WE was 8μg·mL-1.Eurycomanone had a good inhibitory effect on xanthine oxidase,the molecular docking energy was-5.57 kcal·mol-1.Network pharmacology found that NFAT5 and IGF1R were common targets among eurycomanone,hyperuricemia and inflammation,eurycomanone and two target proteins had low docking energy(-2.88 kcal·mol-1 and-4.01 kcal·mol-1).CONCLUSION The material basis of E.longifoliain improving hyperuricemia is related to eurycomanone and its analogues,and its mechanism may be related to the inhibition of xanthine oxidase activity and the two target proteins NFAT5 and IGF1R in the inflammatory pathway.