State Key Laboratory of Functions and Applications of Medicinal Plants & School of Pharmacy, Guizhou Medical University, Gui-an New District, 550025, Guizhou, China; University Engineering Research Center for the Prevention and Treatment of Chronic Diseases by Authentic Medicinal Materials in Guizhou Province, Gui-an New District, 550025, Guizhou, China; Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guiyang, 550004, Guizhou, China.
Guiyang Xintian Pharmaceutical Co., Ltd, Guiyang, 550000, Guizhou, China.
Biochem Biophys Res Commun. 2024 Jul 5;716:150038. doi: 10.1016/j.bbrc.2024.150038. Epub 2024 Apr 30.
Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1β in the kidney. Harp was a promising anti-HUA agent.
高尿酸血症（HUA）是由于尿酸（UA）合成增加和/或排泄不足引起的。长期的 HUA 可能导致多种疾病，包括痛风和肾损伤。哈巴俄苷（Harp）是从玄参科植物胡黄连中提取的一种具有强大抗炎活性的生物活性化合物。然而，其对 HUA 的潜在作用尚未报道。通过生化和组织学分析评估 Harp 对 HUA 小鼠的抗 HUA 和肾脏保护作用。研究负责 UA 产生和转运的蛋白质，以阐明其抗 HUA 机制，同时评估与 NF-κB/NLRP3 通路相关的蛋白质，以揭示其肾脏保护机制。通过测试其对体重和器官系数的影响来评估安全性。结果表明，Harp 显著降低了 SUA 水平，保护了肾脏免受 HUA 诱导的损伤，但对安全性没有负面影响。在机制上，Harp 通过作为黄嘌呤氧化酶（XOD）和腺苷脱氨酶（ADA）的抑制剂显著减少 UA 的产生，并通过作为 ABCG2、OAT1 的激活剂和 GLUT9 和 URAT1 的抑制剂来减少 UA 的排泄。此外，Harp 显著减少了炎性细胞的浸润，并下调了肾脏中 TNF-α、NF-κB、NLRP3 和 IL-1β 的表达。Harp 是一种有前途的抗 HUA 药物。
