Original Research
DOI DOI: 10.65239/botanicaldrugs.2026.03

Salidroside Improves Hyperuricemia by Simultaneously Regulating Uric Acid Production and Excretion

Shaoshi Zhang1, Shun-Dan Li2, Dong Chang3, Ming‑Yue Wang2, Meng‑Fei An4, Si-Jia Fu5, Ting-Ting Jiang5, Jun Sheng6, Yun‑Li Zhao2, Xuan-Jun Wang4
  1. 1 Yunnan Agricultural University, China
  2. 2 Key Laboratory of Pu-erh Tea Science, Ministry of Education, College of Science, College of Food Science and Technology, Yunnan Agricultural University, China
  3. 3 Yunnan Academy of Scientific & Technical Information, China
  4. 4 College of Agronomy, Chuxiong Normal University, China
  5. 5 College of Agronomy, Chuxiong Normal University
  6. 6 Key Laboratory of Pu-erh Tea Science, Ministry of Education, College of Science, College of Food Science and Technology, Yunnan Agricultural University

Abstract

Background: Hyperuricemia is a common metabolic disease, which seriously affects the quality of life of patients. Salidroside (SAL) is a natural phenolic product extracted from Rhodiola rosea root, which is not only less toxic, but also beneficial for metabolic diseases.

Purpose: To investigate SAL's role in regulating hyperuricemia and explore the potential mechanism.

Methods: Molecular simulation was employed to predict the correlation between SAL and TLR4-NLRP3 pathway. The therapeutic effects of SAL were evaluated in cell model and hyperuricemia mice induced by potassium oxonate and hypoxanthine. Then, the mechanism was explored using Western blot assay.

Results: Prediction results showed that SAL bound stably to target proteins TLR4, NLRP3, Caspase-1, and IL-1β involved in the classical pathway of hyperuricemia TLR4-NLRP3. Further hyperuricemia cell and mice models all showed SAL treatment did decrease the uric acid, creatinine and blood urea nitrogen level. Importantly, pathological observation demonstrated liver and kidney injuries were rescued using HE examination and renal fibrosis ameliorated by Masson staining, which was superior to the positive allopurinol. In terms of mechanism, proteins related to uric acid production (XOD) and excretion (ABCG2, OAT1, OCT1, URAT1 and GLUT9) as well as TLR4-NLRP3 pathway in cell model and hyperuricemia mice were all recovered after SAL administration, which were consistent with the molecular docking prediction.

Conclusion: SAL may serve as a natural small molecule compound for improving hyperuricemia and its associated complications by inhibiting hepatic uric acid production and enhancing renal uric acid excretion. This discovery provides novel insights into hyperuricemia treatment.

How to Cite

1.
Zhang S, Li S-D, Chang D, Wang M, An M, Fu S-J, et al. Salidroside Improves Hyperuricemia by Simultaneously Regulating Uric Acid Production and Excretion. Botanical Drugs [Internet]. 2026 Apr. 8 [cited 2026 Jul. 12];1:21-39. Available from: https://botanicaldrugs.org/index.php/pub/article/view/10
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