Integrating multi-level interactive network and in vivo/vitro studies to explore the protective mechanism of...

The strategies or drugs for preventing and treating Hyperuricemia (HUA) are still lacking. As a traditional Chinese medicine (TCM) with a profound history, Ampelopsis grossedentata has been shown to play diverse biological roles. The purpose of the present study was to evaluate hypouricemic effect of A. grossedentata, and investigate its involved material basis and mechanism. A HUA mice model was established to evaluate the therapeutic effects of A. grossedentata. And then some extracts from A. grossedentata were prepared, isolated and analyzed. Furthermore, network pharmacology, based on the above results, was used to discover potential active ingredients and therapeutic targets, and they were further verified and explored by molecular docking and in vitro experiments. In vivo experiments showed that A. grossedentata exerted hypouricemic effect on mice of HUA. The core active ingredients (quercetin, myricetin and dihydromyricetin etc.) and core targets (PTGS2, XOD and ABCG2 etc.) for A. grossedentata to treat HUA were predicted by network pharmacology. And molecular docking showed that the spontaneous binding activities of above components and targets were marvelous. In vitro experiments further demonstrated that A. grossedentata exerted hypouricemic effect by decreasing the levels of UA, XOD, antioxidant factors, inflammatory factors, GLUT9 and URAT1 in HK-2 cells of HUA. Taken together, this study integrates multi-level interaction network with in vivo/vitro experiments to systematically reveal the material basis and mechanism of A. grossedentata in treating HUA, which provides a scientific basis for further study of A. grossedentata and HUA.