Zhou Haifeng, Yue Xinyi, Shen Longhai, Wu Lifeng, Li Xiaobo, Wu Tong
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 201203, China.
Molecules. 2025 Jul 24;30(15):3098. doi: 10.3390/molecules30153098.
(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury.
(1) 背景：研究了从[具体来源未给出]中分离出的三种环烯醚萜苷（羟基马桑毒素、羟基马桑毒素甲酯和马桑苷）的降尿酸作用及其对高尿酸血症诱导的肾损伤的保护作用，实验采用大鼠模型。(2) 方法：通过腹腔注射氧嗪酸钾（PO）和灌胃腺嘌呤，在2周内建立Sprague-Dawley（SD）大鼠高尿酸血症（HUA）模型。随后，药物干预组的大鼠以40 mg/kg/天的浓度接受相应药物治疗，持续7天。(3) 结果：结果表明，三种化合物降低了血清尿酸（SU）、肌酐（CRE）和血尿素氮（BUN）水平，同时尿酸、尿尿素氮和肌酐的尿排泄水平增加。此外，三种环烯醚萜苷的给药增强了肾滤过能力，表现为24小时肌酐清除率（CCR）和24小时尿酸清除率（CUA）升高；改善了尿酸排泄分数（FEUA）；并减轻了肾损伤。最后，三种环烯醚萜苷通过下调URAT1和GLUT9以及上调ABCG2、OAT1和OAT3促进HUA大鼠的尿酸排泄。此外，分子对接结果进一步证实了这三种化合物可通过氢键、P-π键和疏水键与尿酸转运体的多个位点结合这一发现。(4) 结论：发现三种环烯醚萜苷通过增加尿酸排泄来降低SU水平。它们是预防HUA和HUA诱导的肾损伤的有前景的天然产物。
