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Shen-Shuai-II-Recipe inhibits aerobic glycolysis through SIRT1 in 5/6 ablation/infarction renal failure model
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  • Published: 11 January 2026

Shen-Shuai-II-Recipe inhibits aerobic glycolysis through SIRT1 in 5/6 ablation/infarction renal failure model

  • Tianying Lan1,4,5,6 na1,
  • Xinyue Zhang2 na1,
  • Xiao Lyu1,4,5,6,
  • Ming Wu1,4,5,6,
  • Chen Wang1,4,5,6 &
  • …
  • Liuyi Yang3 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Nephrology
  • Pathogenesis

Abstract

Renal fibrosis is the common pathological feature of chronic kidney diseases, which is in parallel with increasing energy demand in proximal tubular epithelial cells during the metabolic shift from fatty acid oxidation to glycolysis. Shen-Shuai-II-Recipe (SSR) is a traditional Chinese medicine formula with known renal benefits in patients with chronic kidney disease (CKD) and has been shown to intervene in renal energy metabolism in a rodent model of CKD. We aimed to explore the mechanism underlying the protective effect of SSR against CKD. A 5/6 ablation/infarction (A/I) renal failure model was established in rats, followed by 8 weeks of gavage feeding with SSR or Losartan, a positive control. For in vitro experiments, normal rat kidney-52E (NRK-52E) cells were cultured under hypoxic condition (1% O2) or normoxic condition. The expression of fibrotic markers and aerobic glycolysis-related enzymes were determined by Western blotting analysis. The concentration of metabolites was also measured. The concentration of lactic acid was increased, and the concentration of pyruvic acid was decreased in vitro and in vivo models, which were correlated with increased expression of glycolysis-related enzymes Hexokinase2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), SSR treatment reversed the changes of renal glycolysis in cells and animals, which was associated with reduced expression of fibrotic markers such as fibronectin and α-SMA. Mechanistically, SSR treatment enhanced the expression of Sirtuin 1 (SIRT1) and reduced the expression of Hypoxia-Inducible Factor 1-alpha (HIF-1α) in vitro and in vivo models. Downregulation of SIRT1 by small interfering ribonucleic acid (siRNA) reversed the anti-fibrotic effect and anti-glycolysis effect of SSR in renal cells. SSR exerts an anti-fibrotic effect and inhibits renal aerobic glycolysis in CKD via the regulation of SIRT1/HIF-1α.

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Data availability

All data supporting the findings of this study are available within the paper and its Supplementary Information.

References

  1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 105, S117–S314. https://doi.org/10.1016/j.kint.2023.10.018 (2024).

    Google Scholar 

  2. Charles, C. & Ferris, A. H. Chronic kidney disease. Prim. Care. 47, 585–595. https://doi.org/10.1016/j.pop.2020.08.001 (2020).

    Google Scholar 

  3. Liu, B. C., Tang, T. T., Lv, L. L. & Lan, H. Y. Renal tubule injury: a driving force toward chronic kidney disease. Kidney Int. 93, 568–579. https://doi.org/10.1016/j.kint.2017.09.033 (2018).

    Google Scholar 

  4. Flythe, J. E. & Watnick, S. Dialysis for chronic kidney failure: a review. JAMA 332, 1559–1573. https://doi.org/10.1001/jama.2024.16338 (2024).

    Google Scholar 

  5. Ortiz, A. et al. Board of the EURECA-m working group of ERA-EDTA. Epidemiology, contributors to, and clinical trials of mortality risk in chronic kidney failure. Lancet 383, 1831–1843. https://doi.org/10.1016/S0140-6736(14)60384-6 (2014).

    Google Scholar 

  6. Friedman, S. L., Sheppard, D., Duffield, J. S. & Violette, S. Therapy for fibrotic diseases: nearing the starting line. Sci. Transl. Med. 5, 167sr1. https://doi.org/10.1126/scitranslmed.3004700 (2013).

    Google Scholar 

  7. Huang, R., Fu, P. & Ma, L. Kidney fibrosis: from mechanisms to therapeutic medicines. Signal. Transduct. Target. Ther. 8, 129. https://doi.org/10.1038/s41392-023-01379-7 (2023).

    Google Scholar 

  8. Liu, B. C., Tang, T. T., Lv, L. L. & Lan, L. L. H. Y. Renal tubule injury: a driving force toward chronic kidney disease. Kidney Int. 93, 568–579. https://doi.org/10.1016/j.kint.2017.09.033 (2018).

    Google Scholar 

  9. Wang, W. et al. Metabolic reprogramming and renal fibrosis: what role might Chinese medicine play? Chin. Med. 19, 148. https://doi.org/10.1186/s13020-024-01004-x (2024).

  10. Kang, H. M. et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat. Med. 21, 37-46. https://doi.org/10.1038/nm.376220 (2015).

  11. Dhillon, P. et al. The nuclear receptor ESRRA protects from kidney disease by coupling metabolism and differentiation. Cell Metabol. 33, 379–394e378. https://doi.org/10.1016/j.cmet.2020.11.011 (2021).

    Google Scholar 

  12. Wei, X., Hou, Y., Long, M., Jiang, L. & Du, Y. Advances in energy metabolism in renal fibrosis. Life Sci. 312, 121033. https://doi.org/10.1016/j.lfs.2022.121033 (2023).

  13. Yang, S. et al. Inhibition of PFKP in renal tubular epithelial cell restrains TGF-β induced glycolysis and renal fibrosis. Cell Death Dis. 14, 816. https://doi.org/10.1038/s41419-023-06347-1 (2023).

  14. Wei, Q. et al. Glycolysis inhibitors suppress renal interstitial fibrosis via divergent effects on fibroblasts and tubular cells. Am. J. Physiol. Ren. Physiol. 316, F1162–f1172. https://doi.org/10.1152/ajprenal.00422.2018 (2019).

    Google Scholar 

  15. Cai, T. et al. Sodium-glucose cotransporter 2 Inhibition suppresses HIF-1α-mediated metabolic switch from lipid oxidation to Glycolysis in kidney tubule cells of diabetic mice. Cell. Death Dis. 11, 390. https://doi.org/10.1038/s41419-020-2544-7 (2020).

    Google Scholar 

  16. Hewitson, T. D. & Smith, E. R. A metabolic reprogramming of Glycolysis and glutamine metabolism is a requisite for renal fibrogenesis-why and how? Front. Physiol. 12, 645857. https://doi.org/10.3389/fphys.2021.645857 (2021).

    Google Scholar 

  17. Van der Rijt, S., Leemans, J. C., Florquin, S., Houtkooper, R. H. & Tammaro, A. Immunometabolic rewiring of tubular epithelial cells in kidney disease. Nat. Rev. Nephrol. 18, 588–603. https://doi.org/10.1038/s41581-022-00592-x (2022).

    Google Scholar 

  18. Wei, X., Hou, Y., Long, M., Jiang, L. & Du, Y. Molecular mechanisms underlying the role of hypoxia-inducible factor-1 α in metabolic reprogramming in renal fibrosis. Front. Endocrinol. (Lausanne). 13, 927329. https://doi.org/10.3389/fendo.2022.927329 (2022).

    Google Scholar 

  19. Liu, D. et al. HIF-1α: a potential therapeutic opportunity in renal fibrosis. Chem. Biol. Interact. 387, 110808. https://doi.org/10.1016/j.cbi.2023.110808 (2024).

    Google Scholar 

  20. Joo, H. Y. et al. Lee. NADH elevation during chronic hypoxia leads to VHL-mediated HIF-1α degradation via SIRT1 Inhibition. Cell. Biosci. 13, 182. https://doi.org/10.1186/s13578-023-01130-3 (2023).

    Google Scholar 

  21. Lim, J. H. et al. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol. Cell. 38, 864–878. https://doi.org/10.1016/j.molcel.2010.05.023 (2010).

    Google Scholar 

  22. Ryu, D. R. et al. Sirt1-hypoxia-inducible factor-1α interaction is a key mediator of tubulointerstitial damage in the aged kidney. Aging Cell. 18, e12904. https://doi.org/10.1111/acel.12904 (2019).

    Google Scholar 

  23. Yang, J., Yan, R. J., Wang, C. & HE, L. Q. Effects of meliorated renal failure Decoction on renal function and inflammatory cytokines in patients with chronic kidney disease at 3–4 stage. Chin. J. Inform. Tradit. Chin. Med. 21 (12), 15–18 (2014).

    Google Scholar 

  24. Xu, Y. Y., He, Z., Zhou, Y., Yang, J. & Wang, C. Effects of the meliorated renal failure Decoction combined with Western medicine on renal function and renal perfusion in primary chronic kidney disease 3 or 4 stage patients. J. Tradit. Chin. Med. 59, 1480–1484. https://doi.org/10.13288/j.11-2166/r.2018.17.010 (2018). [Chinese].

    Google Scholar 

  25. Wang, M., Yang, J., Zhou, Y. & Wang, C. ShenShuai II recipe attenuates apoptosis and renal fibrosis in chronic kidney disease by increasing renal blood flow and improving oxygen consumption. Evid. Based Complement. Alternat Med. 13, 7602962. https://doi.org/10.1155/2018/7602962 (2018).

    Google Scholar 

  26. Wang, M. et al. Shen Shuai II recipe attenuates renal fibrosis in chronic kidney disease by improving hypoxia-induced the imbalance of mitochondrial dynamics via PGC-1α activation. Phytomedicine 98, 153947. https://doi.org/10.1016/j.phymed.2022.153947 (2022).

  27. Wang, L., Feng, X., Ye, C., Wang, C. & Wang, M. Shen Shuai II recipe inhibits hypoxia-induced Glycolysis by preserving mitochondrial dynamics to attenuate kidney fibrosis. J. Ethnopharmacol. 308, 116271. https://doi.org/10.1016/j.jep.2023.116271 (2023).

    Google Scholar 

  28. Hong, Y. A., Kim, J. E., JO, M. & Ko, G. J. The role of sirtuins in kidney diseases. Int. J. Mol. Sci. 21, 6686. https://doi.org/10.3390/ijms21186686 (2020).

    Google Scholar 

  29. Morigi, M., Perico, L. & Benigni, A. Sirtuins in renal health and disease. J. Am. Soc. Nephrol. 29, 1799–1809. https://doi.org/10.1681/ASN.2017111218 (2018).

    Google Scholar 

  30. Han, X. et al. Targeting Sirtuin1 to treat aging-related tissue fibrosis: from prevention to therapy. Pharmacol. Ther. 229, 107983. https://doi.org/10.1016/j.pharmthera.2021.107983 (2022).

    Google Scholar 

  31. Wu, H. et al. Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming. Nat. Commun. 14, 6858. https://doi.org/10.1038/s41467-023-42634-3 (2023).

    Google Scholar 

  32. Owczarek, A. et al. Melatonin lowers HIF-1α content in human proximal tubular cells (HK-2) due to preventing its deacetylation by sirtuin 1. Front. Physiol. 11, 572911. https://doi.org/10.3389/fphys.2020.572911 (2020).

  33. Sun, X. H. et al. Connexin 43 prevents the progression of diabetic renal tubulointerstitial fibrosis by regulating the SIRT1-HIF-1α signaling pathway. Clin. Sci. (Lond.) 134, 1573–1592. https://doi.org/10.1042/CS20200171 (2020).

    Google Scholar 

  34. Yang, L. Y. et al. Shen Shuai II Recipe attenuates renal interstitial fibrosis by improving hypoxia via the IL-1β/c-Myc pathway. Evid. Based Complement Alternat. Med. 7, 5539584. https://doi.org/10.1155/2021/5539584 (2021).

  35. He, Y. et al. Salvianolic acid B attenuates epithelial-mesenchymal transition in renal fibrosis rats through activating Sirt1-mediated autophagy. Biomed. Pharmacother. 128, 110241. https://doi.org/10.1016/j.biopha.2020.110241 (2020).

    Google Scholar 

  36. Poudel, A. et al. Berberine hydrochloride protects against cytokine-induced inflammation through multiple pathways in undifferentiated C2C12 myoblast cells. Can. J. Physiol. Pharmacol. 97, 699–707. https://doi.org/10.1139/cjpp-2018-0653 (2019).

  37. Mehdi, S., Mehmood, M. H., Ahmed, M. G. & Ashfaq, U. A. Antidiabetic activity of berberis brandisiana is possibly mediated through modulation of insulin signaling pathway, inflammatory cytokines and adipocytokines in high fat diet and streptozotocin-administered rats. Front. Pharmacol. 14, 1085013. https://doi.org/10.3389/fphar.2023.1085013 (2023).

    Google Scholar 

  38. Zhao, Y., Yang, W., Zhang, X., Lv, C. & Lu, J. Icariin, the main prenylflavonoid of epimedii Folium, ameliorated chronic kidney disease by modulating energy metabolism via AMPK activation. J. Ethnopharmacol. 312, 116543. https://doi.org/10.1016/j.jep.2023.116543 (2023).

    Google Scholar 

  39. Wu, S. et al. Tanshinone IIA ameliorates experimental diabetic cardiomyopathy by inhibiting Endoplasmic reticulum stress in cardiomyocytes via SIRT1. Phytother. Res. 37, 3543–3558. https://doi.org/10.1002/ptr.7831 (2023).

    Google Scholar 

  40. Bei, Y. et al. Anti-influenza A virus effects and mechanisms of emodin and its analogs via regulating PPARα/γ-AMPK-SIRT1 pathway and fatty acid metabolism. Biomed. Res. Int. 2021, 9066938. https://doi.org/10.1155/2021/9066938 (2021).

  41. Cui, J., Wang, S., Bi, S., Zhou, H. & Sun, L. Emodin-based regulation and control of serum complement C5a, oxidative stress, and inflammatory responses in rats with Urosepsis via AMPK/SIRT1. Iran. J. Allergy Asthma Immunol. 23, 550–562. https://doi.org/10.18502/ijaai.v23i5.16750 (2024).

    Google Scholar 

  42. Zhao, M. et al. Salvianolic acid B regulates macrophage polarization in ischemic/reperfused hearts by inhibiting mTORC1-induced Glycolysis. Eur. J. Pharmacol. 871, 172916. https://doi.org/10.1016/j.ejphar.2020.172916 (2020).

    Google Scholar 

  43. Cui, K. et al. The mixture of ferulic acid and P-Coumaric acid suppresses colorectal cancer through LncRNA 495810/PKM2 mediated aerobic Glycolysis. Int. J. Mol. Sci. 23, 12106. https://doi.org/10.3390/ijms232012106 (2022).

    Google Scholar 

  44. Liu, J. et al. Icariin ameliorates glycolytic dysfunction in alzheimer’s disease models by activating the Wnt/β-catenin signaling pathway. FEBS J. 291, 2221–2241. https://doi.org/10.1111/febs.17099 (2024).

    Google Scholar 

  45. Li, M. et al. Tanshinone IIA inhibits oral squamous cell carcinoma via reducing Akt-c-Myc signaling-mediated aerobic glycolysis. Cell. Death Dis. 11, 381. https://doi.org/10.1038/s41419-020-2579-9 (2020).

    Google Scholar 

  46. Wang, K. J. et al. Emodin induced necroptosis and inhibited glycolysis in the renal cancer cells by enhancing ROS. Oxid. Med. Cell. Longev. 19, 8840590. https://doi.org/10.1155/2021/8840590 (2021).

    Google Scholar 

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Funding

This work was financially supported by Youth Fund of the National Natural Science Foundation of China (No. 82205018) to Liuyi Yang, National Natural Science Foundation of China (No. 81973770) to Chen Wang.

Author information

Author notes

  1. Tianying Lan and Xinyue Zhang contributed equally to this work.

Authors and Affiliations

  1. Nephrology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Tianying Lan, Xiao Lyu, Ming Wu & Chen Wang

  2. Nephrology, Shanghai Seventh People’s Hospital, Shanghai, China

    Xinyue Zhang

  3. Nephrology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China

    Liuyi Yang

  4. Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China

    Tianying Lan, Xiao Lyu, Ming Wu & Chen Wang

  5. Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China

    Tianying Lan, Xiao Lyu, Ming Wu & Chen Wang

  6. TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China

    Tianying Lan, Xiao Lyu, Ming Wu & Chen Wang

Authors
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Contributions

L performance for in vitro and in vivo experiments, Data analysis, Manuscript drafting. Z performance for in vivo experiments, Data analysis. L performance for in vivo experiments, Data analysis. W performance for manuscript drafting, Supervision. W performance for Conceptualization, experimental design. Y performance for Conceptualization, Data analysis, Performance for in vitro and in vivo experiments, Manuscript drafting, Project managing.

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Correspondence to Chen Wang or Liuyi Yang.

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Lan, T., Zhang, X., Lyu, X. et al. Shen-Shuai-II-Recipe inhibits aerobic glycolysis through SIRT1 in 5/6 ablation/infarction renal failure model. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35061-z

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  • Received: 24 June 2025

  • Accepted: 01 January 2026

  • Published: 11 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-35061-z

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Keywords

  • SIRT1
  • Aerobic glycolysis
  • Renal fibrosis
  • CKD
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