Polydatin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation by inhibiting NF-κB/NLRP3 inflammasome activation via the AMPK/SIRT1 pathway.

Abstract

This study was designed to investigate the effects of polydatin (PLD) on potassium oxonate-induced hyperuricemic rats. Hyperuricemic rats were treated with potassium oxonate (250 mg kg-1) intragastrically for 7 days, and polydatin (25, 50 mg kg-1) or allopurinol (5 mg kg-1) was administered to the rats 1 h after the potassium oxonate exposure. Polydatin administration decreased the levels of uric acid and creatinine in serum and urine, leading to inhibition of pro-inflammatory cytokine production in serum and kidney. Western blot analyses illustrated that polydatin down-regulated the translocation of NF-κB p65, the degradation of IκBα, and the protein levels of inflammasome components (NLRP3, ASC, and caspase-1), which led to reduced IL-1β secretion. Notably, polydatin treatment activated AMP kinase (AMPK) protein and increased SIRT1 expression. Taken together, polydatin might be a promising agent for gouty treatment to inhibit renal NF-κB/NLRP3 inflammasome activation via the AMPK/SIRT1 pathway.