Gardenia jasminoides Ellis 70% ethanolic fraction alleviates hyperuricemia by upregulating PPARγ and modulating its downstream urate transporters and anti-inflammatory pathways

Ethnopharmacological relevance Gardenia jasminoides Ellis (GJE) is a traditional Chinese medicine widely used for metabolic disorders. However, its efficacy against hyperuricemia, the responsible active fraction, and the underlying mechanisms of its effect remains to be clarified. Aim of the study To investigate the material basis and urate-lowering activity of the 70% ethanolic fraction of GJE (GJE70), and to elucidate its molecular mechanism. Materials and methods UPLC-Q-TOF-MS characterized the chemical composition of GJE70. Hyperuricemia was induced in rats by potassium oxonate and yeast extract. Serum and urinary uric acid, uric acid clearance, renal function, and histopathology were assessed for anti-hyperuricemia efficacy and urate excretion. Hepatic function and histology were examined for safety. To explore mechanisms, kidney transcriptomics and metabolomics were performed; molecular docking predicted compound-target binding, which was validated by IF, WB, qRT-PCR and rescue experiments in HK-2 cells. Results UPLC-Q-TOF-MS identified 18 major compounds in GJE70, with crocins predominant. In hyperuricemia rats, GJE70 significantly reduced serum uric acid and increased urinary uric acid excretion and clearance, indicating enhanced renal urate elimination. Renal function and histopathology showed alleviated renal injury without obvious hepatotoxicity, with normal liver enzymes and histology. Transcriptomic and metabolomic analyses revealed that GJE70 mainly modulated PPAR signaling pathways. Molecular docking and MD Analysis demonstrated strong binding affinities of compounds to PPARγ. Subsequent IF, WB, and qRT-PCR confirmed that GJE70 upregulated PPARγ expression and its downstream urate transporters (ABCG2, OAT1, and OAT3), and suppressed NF-κB signaling levels. In HK-2 cells, GJE70 reduced supernatant uric acid, upregulated ABCG2/OAT1/OAT3, and inhibited NF-κB activation; GW9662 attenuated these effects, confirming PPARγ dependence. Conclusion GJE70 exerts potent urate-lowering and renoprotective effects via PPARγ-mediated regulation of urate transporters and anti-inflammatory pathways, suggesting its potential as a therapeutic candidate for hyperuricemia. Download: Download high-res image (445KB) Download: Download full-size image