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

Abstract

Hyperuricemia (HUA), a serious metabolic disease that manifests as an elevated serum uric acid (SUA) level, is closely related to gout, hypertension, diabetes, coronary heart disease, chronic kidney disease, and other conditions. Here, we have investigated the potential of kaemperide, a natural flavonoid, in the treatment of HUA based on a kidney-on-a-chip for the first time. The result reveals that kaemperide enhances cell viability, alleviates the UA-induced inflammatory response and promotes UA excretion significantly. Through network pharmacology analysis, URAT1, an important uric acid transporter, is identified as the potential target of kaemperide. Immunofluorescence analysis and surface plasmon resonance confirm a strong, dose-dependent binding between kaemperide and URAT1. Additionally, molecular docking elucidates the specific interaction sites and binding mechanism, and immunofluorescence analysis operated in the kidney-on-a-chip verifies the binding interaction model. In summary, this study demonstrates kaemperide as a promising HUA drug candidate for the first time, and provides a good experimental platform for the nephropathy studies and corresponding drug screening.