- 期刊Journal of ethnopharmacology（J Ethnopharmacol）
- 发表时间2026-10-11
- 作者Li R, Chen G, Li Y, Liu H, Huang L, Yang C, Rao Y
- 卷期页码122492
- DOI10.1016/j.jep.2026.122492
- PMID42860231
摘要机译
【ETHNOPHARMACOLOGICAL相关性】栀子（GJE）是一种广泛用于代谢紊乱的中药，但其抗高尿酸血症的疗效、负责任的活性组分及其作用的潜在机制仍有待阐明。【研究目的】探讨GJE 70%乙醇组分（GJE70）的物质基础和降尿酸活性，并阐明其分子机制。
[材料与方法]UPLC-Q-TOF-MS对GJE70的化学成分进行了表征。用牛磺酸钾和酵母提取物诱导大鼠高尿酸血症。评估血清和尿酸、尿酸清除率、肾功能和组织病理学对抗高尿酸血症的疗效和尿酸排泄率。检查肝脏功能和组织学以确定安全性。为了探索机制，进行了肾脏转录组学和代谢组学；
分子对接预测化合物-靶点结合，并通过IF、WB、qRT-PCR和HK-2细胞的救援实验得到验证。[结果]UPLC-Q-TOF-MS在GJE70中鉴定出18种主要化合物，以鳄鱼蛋白为主。在高尿酸血症大鼠中，GJE70显著降低血清尿酸，增加尿酸排泄和清除，表明肾尿酸清除增强。
肾功能和组织病理学显示肾损伤减轻，无明显肝毒性，肝酶和组织学正常，转录组学和代谢组学分析显示GJE70主要调节PPAR信号通路，分子对接和MD分析显示化合物与PPARγ有很强的结合亲和力。
随后的IF、WB和qRT-PCR证实GJE70上调PPARγ表达及其下游尿酸转运蛋白（ABCG2、OAT1和OAT3），抑制NF-κB信号转导水平。在HK-2细胞中，GJE70降低上清液尿酸，上调ABCG2/OAT1/OAT3，抑制NF-κB激活；GW9662减弱这些作用，证实PPARγ依赖。
[结论]GJE70通过PPARγ介导的尿酸转运蛋白和抗炎途径发挥有效的降尿酸和肾保护作用，提示其作为高尿酸血症治疗候选药物的潜力。
展开英文摘要原文
【ETHNOPHARMACOLOGICAL RELEVANCE】Gardenia jasminoides Ellis (GJE) is a traditional Chinese medicine widely used for metabolic disorders. However, its efficacy against hyperuricemia, the responsible active fraction, and the underlying mechanisms of its effect remains to be clarified.
【AIM OF THE STUDY】To investigate the material basis and urate-lowering activity of the 70% ethanolic fraction of GJE (GJE70), and to elucidate its molecular mechanism.
【MATERIALS AND METHODS】UPLC-Q-TOF-MS characterized the chemical composition of GJE70. Hyperuricemia was induced in rats by potassium oxonate and yeast extract. Serum and urinary uric acid, uric acid clearance, renal function, and histopathology were assessed for anti-hyperuricemia efficacy and urate excretion. Hepatic function and histology were examined for safety. To explore mechanisms, kidney transcriptomics and metabolomics were performed; molecular docking predicted compound-target binding, which was validated by IF, WB, qRT-PCR and rescue experiments in HK-2 cells.
【RESULTS】UPLC-Q-TOF-MS identified 18 major compounds in GJE70, with crocins predominant. In hyperuricemia rats, GJE70 significantly reduced serum uric acid and increased urinary uric acid excretion and clearance, indicating enhanced renal urate elimination. Renal function and histopathology showed alleviated renal injury without obvious hepatotoxicity, with normal liver enzymes and histology. Transcriptomic and metabolomic analyses revealed that GJE70 mainly modulated PPAR signaling pathways. Molecular docking and MD Analysis demonstrated strong binding affinities of compounds to PPARγ. Subsequent IF, WB, and qRT-PCR confirmed that GJE70 upregulated PPARγ expression and its downstream urate transporters (ABCG2, OAT1, and OAT3), and suppressed NF-κB signaling levels. In HK-2 cells, GJE70 reduced supernatant uric acid, upregulated ABCG2/OAT1/OAT3, and inhibited NF-κB activation; GW9662 attenuated these effects, confirming PPARγ dependence.
【CONCLUSION】GJE70 exerts potent urate-lowering and renoprotective effects via PPARγ-mediated regulation of urate transporters and anti-inflammatory pathways, suggesting its potential as a therapeutic candidate for hyperuricemia.
相关物质
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