The resveratrol trimer caraphenol A from Caragana sinica alleviates hyperuricemia and hyperuricemia-induced renal injury in mice by modulating uric acid metabolism and inflammatory pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Caragana sinica is a traditional Chinese medicinal long employed for treating hyperuricemia (HUA)-related gout.

AIM OF THE STUDY: To evaluate the hypouricemic and renoprotective effects of caraphenol A (CA), a resveratrol trimer isolated from C. sinica, and to elucidate its underlying molecular mechanisms.

MATERIALS AND

METHODS

HUA was induced in mice using potassium oxonate and hypoxanthine. Therapeutic efficacy was assessed by measuring serum/urine uric acid (UA), creatinine, and blood urea nitrogen levels, alongside renal histopathology. Molecular mechanisms were investigated using transcriptomic analysis, Western blotting, and RT-qPCR.

RESULTS

CA significantly reduced serum UA levels and alleviated renal injury without systemic toxicity. Mechanistically, CA inhibited UA production by suppressing hepatic XOD activity and protein expression. Furthermore, CA restored UA homeostasis by modulating renal transporters (URAT1, GLUT9, OAT1, and ABCG2). Transcriptomic analysis identified 34 pivotal DEGs enriched in the cytokine-cytokine receptor interaction pathway, suggesting that CA protects kidneys by interrupting inflammatory cascades.

CONCLUSION

CA is a promising, safe, and multi-target agent that manages UA and renal injury by coordinately modulating UA metabolism and inflammatory pathways.