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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1394369

Piperazine ferulate inhibits diabetic nephropathy by suppressing AGE/RAGE-mediated inflammatory signaling in rats and podocytes

Provisionally accepted
Xiu-Meng Zhang Xiu-Meng Zhang 1Xin-Ran Min Xin-Ran Min 1Hong-Xiao Xie Hong-Xiao Xie 1Yan-Ning Jiang Yan-Ning Jiang 1Yixin Rui Yixin Rui 1Bo Li Bo Li 2Rong Liu Rong Liu 1*Nan Zeng Nan Zeng 1
  • 1 Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
  • 2 Chengdu Hanpharm Pharmaceutical Co., Ltd, sichusn, China

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

    Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage.Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Method: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley (SD) rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro, rat podocytes were treated with 25 mmol/L glucose and cultured for 24 hours, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucoseinduced podocyte injury in vitro. Regarding molecular mechanisms, our study demonstrated that PF down-regulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN.

    Keywords: AGE-RAGE, diabetic nephropathy, Inflammations, Piperazine ferulate, podocyte

    Received: 01 Mar 2024; Accepted: 05 Jul 2024.

    Copyright: © 2024 Zhang, Min, Xie, Jiang, Rui, Li, Liu and Zeng. 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: Rong Liu, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.