高尿酸血症(HUA),由尿酸(UA)过量产生或排泄减少引起的代谢性疾病,据报道,与各种UA转运蛋白密切相关。Clerodendranthusspicatus(C.spicatus)是一种在中国广泛用于治疗HUA的草药。然而,机制尚未明确。这里,用10%果糖诱导HUA大鼠模型。生化指标的水平,包括UA,黄嘌呤氧化酶(XOD),腺苷脱氨酶(ADA),血尿素氮(BUN),和肌酐(Cre),被测量。应用蛋白质印迹法探讨其对肾脏UA转运体的影响,如尿酸转运蛋白1(URAT1),葡萄糖转运蛋白9(GLUT9),和ATP结合盒超家族G成员2(ABCG2)。此外,通过代谢组学鉴定了C.spicatus对血浆代谢产物的影响。我们的结果表明C.spicatus可以显着降低血清UA水平,XOD,ADA和Cre,改善HUA大鼠肾脏病理变化。同时,C.spicatus显着抑制URAT1和GLUT9的表达,同时以剂量依赖性方式增加ABCG2的表达。代谢组学显示,13种成分,包括1-棕榈酰-2-花生四酰基-sn-甘油-3-PE,Tyr-Leu和N-顺式-15-四苯酰-C18-鞘氨醇,被鉴定为C.spicatus降低UA作用的潜在生物标志物。此外,途径富集分析表明,精氨酸的生物合成,氨基酸的生物合成,嘧啶代谢和其他代谢途径可能参与C.spicatus对HUA的保护。本研究首次通过分子生物学和代谢组学分析,为HUA的治疗提供了新的思路。
Hyperuricemia (HUA), a metabolic disease caused by excessive production or decreased excretion of uric acid (UA), has been reported to be closely associated with a variety of UA transporters. Clerodendranthus spicatus (C. spicatus) is an herbal widely used in China for the treatment of HUA. However, the mechanism has not been clarified. Here, the rat model of HUA was induced via 10% fructose. The levels of biochemical indicators, including UA, xanthine oxidase (XOD), adenosine deaminase (ADA), blood urea nitrogen (BUN), and creatinine (Cre), were measured. Western blotting was applied to explore its effect on renal UA transporters, such as urate transporter1 (URAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette super-family G member 2 (ABCG2). Furthermore, the effect of C. spicatus on plasma metabolites was identified by metabolomics. Our results showed that C. spicatus could significantly reduce the serum levels of UA, XOD, ADA and Cre, and improve the renal pathological changes in HUA rats. Meanwhile, C. spicatus significantly inhibited the expression of URAT1 and GLUT9, while increased the expression of ABCG2 in a dose-dependent manner. Metabolomics showed that 13 components, including 1-Palmitoyl-2-Arachidonoyl-sn-glycero-3-PE, Tyr-Leu and N-cis-15-Tetracosenoyl-C18-sphingosine, were identified as potential biomarkers for the UA-lowering effect of C. spicatus. In addition, pathway enrichment analysis revealed that arginine biosynthesis, biosynthesis of amino acids, pyrimidine metabolism and other metabolic pathways might be involved in the protection of C. spicatus against HUA. This study is the first to explore the mechanism of anti-HUA of C. spicatus through molecular biology and metabolomics analysis, which provides new ideas for the treatment of HUA.