Original Articles

Mechanic evaluation of Jisheng Shenqi Wan (济生肾气丸) on calcium oxalate kidney stones: an integrated network pharmacology and metabolomics

  • SHI Bing ,
  • LI Yang ,
  • JIANG Zhuocheng ,
  • QIN Guozheng ,
  • ZHAO Fan
Expand
  • 1 Department of Urology, Nantong Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong 226000, China
    2 the First Clinical College, Nanjing University of Chinese Medicine, Nanjing 210000, China
    3 Department of Gynaecology, Nantong Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong 226000, China
    4 Department of Urology, Affiliated Hospital of Nantong University, Nantong 226000, China
    5 Department of Urology and Andrology, the First Affifiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650000, China
Dr. ZHAO Fan, Department of Urology, Affiliated Hospital of Nantong University, Nantong 226000, China;
Prof. QIN Guozheng, the First Clinical College, Nanjing University of Chinese Medicine, Nanjing 210000, China; Department of Urology and Andrology, the First Affifiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650000, China. Telephone: + 86-18752867039

Received date: 2025-02-26

  Accepted date: 2025-06-09

  Online published: 2025-09-29

Supported by

Grant from Jiangsu Provincial Research Hospital(YJXYY202204-YSA05);Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(2023-QNRC2-B21);Nantong University Special Research Fund for Clinical Medicine: Exploring the Mechanism of Jisheng Shenqi Wan in Preventing and Treating Calcium Oxalate Kidney Stones Based on Oxidative Stress and Ferroptosis(2024JQ049);Nantong Social Livelihood Science and Technology Plan Project: Exploring the Mechanism of Jisheng Shenqi Wan in Preventing and Treating Calcium Oxalate Kidney Stones Based on the Concept of “Shen-Kidney Theory”(MS2024013)

Abstract

OBJECTIVE: To understand the efficacy of Jisheng Shenqi Wan (JSSQW, 济生肾气丸) in treating calcium oxalate kidney stones (KS) and to investigate the mechanism of JSSQW action by combining network pharmacology with metabolomics analysis based on ultra-high performance liquid chromatography combined with tandem electrostatic field orbital trap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS).

METHODS: The chemical components of JSSQW absorbed into rat blood were identified by UHPLC-Q/Orbitrap HRMS. The identified components were introduced into the Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine platform to screen for target genes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and disease enrichment analysis. A KS rat model was generated using the oxalic acid precursor method to examine the efficacy of JSSQW for treating KS. Serum metabolomics was used to monitor changes in endogenous substances in KS rats after JSSQW intervention.

RESULTS: Twenty-three chemicals from JSSQW were identified in the blood of JSSQW gavage-administered rats. KEGG enrichment analysis predicted the top 20 signaling pathways affected by these 23 chemicals. Disease enrichment analysis showed that the target genes of these 23 chemicals were enriched in diseases of the urinary system and endocrine system, including kidney stones. In a KS rat model, JSSQW inhibited the aggregation of calcium oxalate crystals, reduced renal tubular injury, lowered the renal index, and improved biochemical indicators (blood creatinine, blood urea nitrogen). Serum metabolomics identified 25 differential metabolites that responded to JSSQW treatment. They were mainly lipids, with phosphatidylethanolamine and phosphorylcholine and their derivatives accounting for the highest proportion. Metabolic pathway analysis showed that the changes in differential metabolites were related to multiple metabolic pathways, especially sphingolipid metabolism and sphingolipid signaling pathways.

CONCLUSIONS: JSSQW can inhibit the aggregation of calcium oxalate crystals in the kidneys, reduce tubular injury, and improve kidney function in KS rats. Its mechanism of action may be related to regulating disordered metabolites and metabolic pathways, especially glycerol phospholipid metabolism, sphingolipid metabolism, and sphingolipid signaling.

Cite this article

SHI Bing , LI Yang , JIANG Zhuocheng , QIN Guozheng , ZHAO Fan . Mechanic evaluation of Jisheng Shenqi Wan (济生肾气丸) on calcium oxalate kidney stones: an integrated network pharmacology and metabolomics[J]. Journal of Traditional Chinese Medicine, 2026 , 46(2) : 371 -381 . DOI: 10.19852/j.cnki.jtcm.20250929.001

References

1. Bishop K, Momah T, Ricks J. Nephrolithiasis. Prim Care 2020; 47: 661-71.
2. Rodgers A, Trinchieri A. Fifty years of basic and clinical renal stone research: have we achieved major breakthroughs? A debate. Curr Opin Nephrol Hypertens 2023; 32: 177-82.
3. Zeng G, Mai Z, Xia S, et al. Prevalence of kidney stones in China: an ultrasonography based cross-sectional study. BJU Int 2017; 120: 109-16.
4. Dong CT, Song C, He ZQ, et al. An overview of global research landscape in etiology of urolithiasis based on bibliometric analysis. Urolithiasis? 2023; 51: 71.
5. Ye Z, Zeng G, Yang H, et al. The status and characteristics of urinary stone composition in China. BJU Int 2020; 125: 801-9.
6. Liu H, Zhang Y. Characteristics of Traditional Chinese Medicine syndromes in 296 patients with urolithiasis. Zhong Guo Shi Yan Fang Ji Xue Za Zhi 2023; 29: 209-15.
7. Wan S, Xu K, Ren LM, et al. Analysis of Traditional Chinese Medicine constitution types among adult urolithiasis patients in Wuhu, China. Altern Ther Health Med 2023; 29: 435-9.
8. Jiang QH, Dong CT, He ZQ, Jiang R, Liao WB, Yang SX. Research landscape and pharmacological mechanisms of Traditional Chinese Medicines in treating and preventing urolithiasis: unearthing an anti-urolithic treasure trove. J Ethnopharmacol 2024; 334: 118502.
9. Shi B, Zhao F, Xie L, et al. Discussion on the prevention and treatment of urolithiasis by integrated Traditional Chinese and Western Medicine based on Shen-kidney theory. Zhong Yi Za Zhi 2024; 65: 572-6, 99.
10. Lin PH, Lin SK, Hsu RJ, Cheng KC, Liu JM. The use and the prescription pattern of Traditional Chinese Medicine among urolithiasis patients in Taiwan: a population-based study. J Altern Complement Med 2016; 22: 88-95.
11. Dong CT, Zhou JW, Su XZ, et al. Understanding formation processes of calcareous nephrolithiasis in renal interstitium and tubule lumen. J Cell Mol Med 2024; 28: e18235.
12. Bao D, Zhang HM, Wang JW, Wang Y, Wang SX, Zhao MH. Determinants on urinary excretion of oxalate and other key factors related to urolithiasis among patients with chronic kidney disease: a single center study. Urolithiasis 2023; 51: 88.
13. Khan A. In vitro and in vivo models for the study of urolithiasis. Urologia 2018; 85: 145-9.
14. Li C. Thoughts on in vitro pharmacological research methods of Chinese herbal compound. Zhong Hua Zhong Yi Yao Za Zhi 2023; 38: 1441-4.
15. Wu JS, Zhang FQ, Li ZZ, Jin WY, Shi Y. Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review. J Tradit Chin Med 2022; 42: 479-86.
16. Duan X, Wang N, Peng D. Application of network pharmacology in synergistic action of Chinese herbal compounds. Theor Biosci 2024; 143: 195-203.
17. Mosley JD, Dunn WB, Kuligowski J, et al. Metabolomics 2023 workshop report: moving toward consensus on best QA/QC practices in LC-MS-based untargeted metabolomics. Metabolomics 2024; 20: 73.
18. Skogvold HB, Sand ES, Elgstoen KBP. Global metabolomics using LC-MS for clinical applications. Methods Mol Biol 2025; 2855: 23-39.
19. Thongprayoon C, Lieske JC, Rule AD, Denic A.Authors' reply: urine metabolomic versus standard chemistry analysis: what can metabolomic analysis bring to the treatment and prevention of urolithiasis? J Am Soc Nephrol 2023; 34: 1124-5.
20. Zhu W, Li H, Zhang M, Ji B, Liu Z. Plasma metabolites as potential markers and targets to prevent and treat urolithiasis: a Mendelian randomization study. Front Mol Biosci 2024; 11: 1426575.
21. Wang R, Qi S, Zhang J, Ren H, Xie L, Liu C. Nontargeted urine metabolomics with electrospray ionization-mass spectrometry reveals the major metabolic characterization between adult males and females involved in calcium oxalate urolithiasis. Anal Lett 2024; 57: 1369-80.
22. Tran TVM, Li X, Adams-Huet B, Maalouf NM. Impact of age and renal function on urine chemistry in patients with calcium oxalate kidney stones. Urolithiasis 2021; 49: 495-504.
23. Tan ZL, Hong J, Sun AC, Ding MD, Shen JW. Causal effects of circulating lipids and lipid-lowering drugs on the risk of urinary stones: a Mendelian randomization study. Front Endocrinol 2023; 14: 1301163.
24. Wang D, Zhang D, Zhang L, Shi F, Zhu Y. Association between triglyceride-glucose index and risk of kidney stone: a Chinese population-based case-control study. BMJ Open 2024; 14: e086641.
25. Kuo A, Hla T. Regulation of cellular and systemic sphingolipid homeostasis. Nat Rev Mol Cell Biol 2024; 25: 802-21.
26. Lee M, Lee SY, Bae Y-S. Functional roles of sphingolipids in immunity and their implication in disease. Exp Mol Med 2023; 55: 1110-30.
27. McCluskey G, Donaghy C, Morrison KE, McConville J, Duddy W, Duguez S. The role of sphingomyelin and ceramide in motor neuron diseases. J Pers Med 2022; 12: 1418.
28. Mallela SK, Merscher S, Fornoni A. Implications of sphingolipid metabolites in kidney diseases. Int J Mol Sci 2022; 23: 4244.
29. Chao YF, Li N, Xiong SL, Zhang GB, Gao SY, Dong X.Lipidomics based on liquid chromatography-high resolution mass spectrometry reveals the protective role of peroxisome proliferator-activated receptor alpha on kidney stone formation in mice treated with glyoxylate. J Sep Sci 2023; 46: e2300452.
30. Chen W, Liu WR, Hou JB, et al. Metabolomic analysis reveals a protective effect of Fu-Fang-Jin-Qian-Chao herbal granules on oxalate-induced kidney injury. Biosci Rep 2019; 39: BSR20181833.
Outlines

/