stilbenes and potassium-oxonate

Previous studies have disclosed the antihyperuricemic effect of polydatin, a natural precursor of resveratrol; however, the mechanisms of action still remain elusive. The present study was undertaken to evaluate the therapeutic effects and the underlying mechanisms of polydatin on potassium oxonate-induced hyperuricemia in rats through metabonomic technology from a holistic view. Nuclear magnetic resonance (NMR) spectroscopy was applied to capture the metabolic changes in sera and urine collected from rats induced by hyperuricemia and polydatin treatment. With multivariate data analysis, significant metabolic perturbations were observed in hyperuricemic rats compared with the healthy controls. A total of eleven and six metabolites were identified as differential metabolites related to hyperuricemia in serum and urine of rats, respectively. The proposed pathways primarily included branched-chain amino acid (BCAA) metabolism, glycolysis, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, purine metabolism, and intestinal microflora metabolism. Additionally, some metabolites indicated the risk of renal injury induced by hyperuricemia. Polydatin significantly lowered the levels of serum uric acid, creatinine, and blood urea nitrogen and alleviated the abnormal metabolic status in hyperuricemic rats by partially restoring the balance of the perturbed metabolic pathways. Our findings shed light on the understanding of the pathophysiological process of hyperuricemia and provided a reference for revealing the metabolic mechanism produced by polydatin in the treatment of hyperuricemia.

Topics: Animals; Blood Urea Nitrogen; Creatinine; Disease Models, Animal; Drugs, Chinese Herbal; Glucosides; Humans; Hyperuricemia; Kidney; Male; Metabolomics; Oxonic Acid; Rats; Rats, Sprague-Dawley; Stilbenes; Uric Acid

Topics: AMP-Activated Protein Kinases; Animals; Glucosides; Humans; Hyperuricemia; Inflammasomes; Kidney; Male; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxonic Acid; Rats; Rats, Sprague-Dawley; Sirtuin 1; Stilbenes

Stilbenes, of which, resveratrol is a representative compound in foods and plants, possess a variety of bioactivities including antioxidation, anti-inflammation, chemoprevention, and cardioprotection. This study was conducted to evaluate the antihyperuricemic and nephroprotective effects of resveratrol and its analogues and explore the possible mechanisms. The structure-activity relationships were analyzed.. Potassium oxonate-induced hyperuricemic mice were dosed by gavage with eight stilbenes. Uric acid, creatinine, and blood urea nitrogen (BUN) levels in serum and urine, clearance rate of creatinine and BUN, 24-h urate excretion, and fractional excretion of uric acid, uromodulin levels in urine and kidney were determined to evaluate renal urate handling and function. Renal protein levels of organic ion transporters were detected to elucidate the possible mechanisms. Resveratrol, trans-4-hydroxystilbene, pterostilbene, polydatin, and mulberroside A were found to have antihyperuricemic activities. These compounds together with trans-2-hydroxystilbene provided nephroprotection. Trans-3,4',5-trimethoxystilbene and cis-combretastatin A-4 had no effects.. The uricosuric and nephroprotective actions of resveratrol and its analogues were mediated by regulating renal organic ion transporters in hyperuricemic mice, supporting their beneficial effects for the prevention of hyperuricemia. The number and position, methoxylation and glycosylation of hydroxyl groups in these trans-stilbenes were required for their effects.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Blood Urea Nitrogen; Carrier Proteins; Creatinine; Disaccharides; Gene Expression Regulation; Glucose Transport Proteins, Facilitative; Glucosides; Gout Suppressants; Hyperuricemia; Kidney; Male; Membrane Proteins; Mice; Mice, Inbred Strains; Octamer Transcription Factor-1; Organic Anion Transport Protein 1; Organic Anion Transporters; Organic Cation Transport Proteins; Organic Cation Transporter 2; Oxonic Acid; Resveratrol; Solute Carrier Family 22 Member 5; Stilbenes; Symporters; Uric Acid