Abstract
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.
Highlights
Hyperuricemia is characterized by a persistent increase of uric acid in circulating blood and is recognized as the key causal precursor in the development of gout [1]
Orally administrated potassium oxonate significantly increased the levels of serum uric acid (SUA), Scr, and blood urea nitrogen (BUN) compared with normal rats. Both polydatin at 50 mg/kg and allopurinol (5 mg/kg) as a positive control significantly reduced the levels of SUA, Scr, and BUN in hyperuricemic rats, consistent with previous studies [14]
These results demonstrated that polydatin exerts beneficial effects on hyperuricemia in rats
Summary
Hyperuricemia is characterized by a persistent increase of uric acid in circulating blood and is recognized as the key causal precursor in the development of gout [1]. Uric acid is produced from the oxidation of hypoxanthine and xanthine catalyzed by xanthine oxidase [4] and is the final product of purine metabolism in humans due to lack of uricase [5]. Either the decreased excretion or the increased production of uric acid may lead to hyperuricemia [6]. Available urate-lowering agents can be grouped by their mechanism of action [8]: xanthine oxidase inhibitors (e.g., allopurinol), uricosuric agents (e.g., benzbromarone), and injectable uricases (e.g., pegloticase). Concern on their tolerability and safety has been raised in recent times with a more attentive evaluation of pharmacovigilance studies [8]. It is urgent to find more effective and safe alternative drugs to manage hyperuricemia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
