Isobavachin Attenuates Renal and Cardiac Injury in Chronic Hyperuricemia via Modulation of NF‐κB and NLRP3 Signaling Pathways

Hyperuricaemia (HUA) is a recognized risk factor for cardiovascular and renal diseases. Isobavachin, a dihydroflavone derivative, demonstrates significant efficacy in reducing uric acid levels. This study investigated the nephroprotective and cardioprotective effects and molecular mechanisms of isobavachin. Through integrative network pharmacology, pathway enrichment analysis, and molecular docking, NF‐κB was identified as a potential target of isobavachin in the context of hyperuricemia‐related cardiac and renal injury. Isobavachin treatment inhibited the activation of the NF‐κB pathway, leading to cytoprotection in uric acid (UA)‐stimulated mRTEC and H9C2 cells. In chronic HUA mice, isobavachin treatment significantly improved renal pathology and reduced renal collagen deposition by inhibiting epithelial‐to‐mesenchymal transition. Isobavachin administration demonstrated therapeutic efficacy in attenuating myocardial injury, hypertrophy, and fibrotic remodeling. Notably, the anti‐inflammatory effects of isobavachin were particularly evident in both renal and cardiac tissues, primarily mediated through its dual regulatory capacity in suppressing NF‐κB pathway activation and NLRP3 inflammasome formation. In conclusion, isobavachin ameliorated cardiac and renal damage caused by chronic HUA, suggesting a new strategy to prevent HUA. Isobavachin alleviates HUA‐induced oxidative stress, inflammation, and fibrosis in the kidney and heart, potentially through its dual role in promoting UA excretion and inhibiting NF‐κB signaling and NLRP3 inflammasome activation.