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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Renal Pharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1611585

Wenyang Jiedu Tongluo Formula Ameliorates Diabetic Kidney Disease by Regulating JAML/SIRT1 Signaling to Improve Lipid Metabolism in db/db Mice

Provisionally accepted
  • 1Changchun University of Chinese Medicine, Changchun, China
  • 2The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin Province, China

The final, formatted version of the article will be published soon.

Introduction: Diabetic kidney disease (DKD), a major microvascular complication of diabetes mellitus, is closely associated with abnormal lipid metabolism, which contributes to secondary renal injury. The JAML/SIRT1 signaling pathway plays a critical role in regulating renal lipid metabolism during DKD progression. To investigate the molecular mechanisms underlying the therapeutic effects of Wenyang Jiedu Tongluo Formula (WYJDTLF) on lipid metabolism in DKD, we conducted an animal study using db/db mice. Methods: The mice were treated with WYJDTLF for 4 weeks, and its efficacy was evaluated through assessments of liver and kidney function, lipid profiles, and renal histopathology. Renal injury was examined using Hematoxylin & Eosin (H&E), Periodic Acid-Schiff (PAS), and Masson's trichrome staining. Podocyte damage was assessed by quantifying the expression of podocyte marker proteins (Nephrin and NPHS2) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, the expression levels of key proteins in the JAML/SIRT1 signaling pathway were analyzed via Western blot (WB).The results demonstrated that WYJDTLF significantly improved liver and kidney function, reduced lipid deposition and inflammatory damage, and alleviated renal fibrosis and pathological injury. These effects were mediated through the regulation of the JAML/SIRT1 signaling pathway. Furthermore, WYJDTLF treatment upregulated the expression of Nephrin and NPHS2, indicating a protective effect on podocyte integrity. Conclusion: Our team has revealed for the first time that the WYJDTLF can improve lipid metabolism abnormalities in db/db mice and alleviate diabetic kidney disease-induced renal pathological damage by inhibiting the JAML/SIRT1 signalling pathway. These findings provide a scientific basis for the potential application of WYJDTLF in the treatment of DKD.

Keywords: Diabetic kidney disease, Lipid Metabolism, Wenyang Jiedu Tongluo Formula, JAML/SIRT1 Signaling Pathway, Traditional Chinese Medicine

Received: 14 Apr 2025; Accepted: 11 Jul 2025.

Copyright: © 2025 Liu, Chang, Li, Cui, Wang, Liu, Cui and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yingzi Cui, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
Shoulin Zhang, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China

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