Investigation on the potential application of kaemperide in hyperuricemia based on kidney-on-a-chip

Abstract

Hyperuricemia (HUA) is a serious metabolic disease with the manifestation of elevated serum uric acid (SUA) level, and closely related to gout, hypertension, diabetes, coronary heart disease, chronic kidney disease, and so on. Here, we have explored the possibility of kaemperide, a natural flavonoid, in HUA treatment based on kidney-on-a-chip for the first time, in which kaemperide shows the ability of imporving cell viability, reducing UA-induced inflammatory response and promoting UA excretion significantly. Through network pharmacology analysis, URAT1, an important uric acid transporter, is orientated and found for kaemperide targets. Immunofluorescence Analysis and Surface Plasmon Resonance demonstrate kaemperide has a strong binding to URAT1 directly with a dose-dependent behavior. And interaction sites and manners are also deciphered by Molecular docking. In summary, this study demonstrates kaemperide as a promising HUA drug candidate firstly, and provides a good experimental platform for the nephropathy studies and corresponding drug screening.