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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 6: 1342 - 1352

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.06.013

Original Articles

Network pharmacology combined with ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method to explore the mechanism of Shizhi Fang (矢志方) in treating uric acid nephropathy mice

  • Feng YANG ,
  • Xuming ZHANG ,
  • Zhiyuan WU ,
  • Jiandong GAO
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  • 1 Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
    2 TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
    3 Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
    4 Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China

Received date: 2024-11-22

  Accepted date: 2025-03-10

  Online published: 2025-11-24

Supported by

Mechanistic Study on How Shizhi Fang Promotes Mitocytosis of Renal Tubular Epithelial Cells to Alleviate Hyperuricemia-Induced Kidney Injury(82274415);Mechanistic Study on Shizhi Fang in Lowering Uric Acid Based on Extracellular Signal-regulated Kinases 1 and 2-mediated Transcriptional Regulation of the Uric Acid Transporter Urate Transporter 1(82474434)

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Abstract

OBJECTIVE: To elucidate the potential mechanisms of Shizhi Fang (SZF, 矢志方) in the treatment of uric acid nephropathy (UAN).

METHODS: SZF-containing serum was prepared from six male rats and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was employed was integrated with UPLC-Q-TOF-MS to predict SZF targets for the treatment of UAN, which were subsequently validated through in vivo experiments. Sixty male Bagg Albino Laboratory-Bred Mouse, substrain c mice were randomly allocated into six groups: Normal, Model, Febuxostat, and three SZF dosage groups. Except for the Normal group, all mice were administered potassium oxonate (250 mg/kg) and adenine (50 mg/kg) via gavage to induce UAN. Four hours post-administration, the Febuxostat group received Febuxostat (6 mg/kg), while the SZF groups received low (0.234 g/kg), medium (0.468 g/kg), or high (0.936 g/kg) doses of SZF. The Normal and Model groups were given an equivalent volume of saline. All treatments were conducted over a period of four weeks. Urine and blood samples were collected for biochemical analysis, and kidney tissues were subjected to histopathological examination and Western blot analysis.

RESULTS: Nine prototype compounds and 30 metabolites were identified in SZF serum. Network pharmacology analysis revealed 195 drug targets and 1608 disease targets, with 76 common drug-disease targets, including signal transducer and activator of transcription 3 (STAT3), proto-oncogene tyrosine-protein kinase Src (SRC), matrix metalloproteinase-9 (MMP9), Caspase 3, and toll-like receptor 4 (TLR4) as key targets. Gene Ontology analysis identified 325 biological processes, 48 cellular components, and 72 molecular functions, while Kyoto Encyclopedia of Genes and Genomes analysis identified 113 pathways. Molecular docking demonstrated strong binding affinities between active compounds and their targets. In the animal study, SZF treatment alleviated pathological damage and improved serum and urine biochemical markers compared to the Model group (P < 0.05, P < 0.01, P < 0.001). Western blot analysis showed a significant reduction in phosphorylated-STAT3, phosphorylated-SRC, MMP9, TLR4, and Caspase3 expression in renal tissues of SZF-treated mice (P < 0.001).

CONCLUSION: SZF may exert therapeutic effects on UAN through multiple targets and pathways.

Key words： uric acid nephropathy; liquid chromatography-mass spectrometry; mechanics; network pharmacology; Shizhi Fang

Cite this article

Feng YANG , Xuming ZHANG , Zhiyuan WU , Jiandong GAO . Network pharmacology combined with ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method to explore the mechanism of Shizhi Fang (矢志方) in treating uric acid nephropathy mice[J]. Journal of Traditional Chinese Medicine, 2025 , 45(6) : 1342 -1352 . DOI: 10.19852/j.cnki.jtcm.2025.06.013

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