School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Oxid Med Cell Longev. 2020 Jul 5;2020:6943860. doi: 10.1155/2020/6943860. eCollection 2020.
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.
先前的研究已经揭示了白藜芦醇的天然前体——虎杖苷具有降血尿酸作用;然而,其作用机制仍不清楚。本研究采用代谢组学技术从整体角度评价虎杖苷对氧嗪酸钾诱导的大鼠高尿酸血症的治疗作用及潜在机制。采用核磁共振(NMR)光谱法检测高尿酸血症大鼠血清和尿液的代谢变化,并结合多元数据分析。与健康对照组相比,高尿酸血症大鼠的代谢发生了显著变化。共鉴定出 11 种血清和 6 种尿液差异代谢物,与大鼠高尿酸血症相关。提出的途径主要包括支链氨基酸(BCAA)代谢、糖酵解、三羧酸循环、酮体的合成与降解、嘌呤代谢和肠道微生物代谢。此外,一些代谢物表明高尿酸血症会导致肾脏损伤。虎杖苷可显著降低血清尿酸、肌酐和血尿素氮水平,并通过部分恢复失调代谢途径的平衡,缓解高尿酸血症大鼠的异常代谢状态。本研究结果阐明了高尿酸血症的病理生理过程,并为揭示虎杖苷治疗高尿酸血症的代谢机制提供了参考。