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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1510098

Yishen Paidu Pills Attenuates 5/6 Nephrectomy Induced Kidney Disease via Inhibiting the PI3K/AKT/mTOR Signaling Pathway

Provisionally accepted
Saiji Liu Saiji Liu Yiling Cao Yiling Cao Qian Yuan Qian Yuan Yaru Xie Yaru Xie Yuting Zhu Yuting Zhu Jun-li Yao Jun-li Yao *Chun Zhang Chun Zhang *
  • Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

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

    Introduction: Chronic kidney disease (CKD) is a substantial global health issue with high morbidity and mortality. Yishen Paidu Pills (YSPDP) are effective concentrated water pills composed of four herbs developed by Wuhan Union Hospital to treat CKD. However, the mechanism of YSPDP action is largely unknown. This study combined metabolomics, network pharmacology, transcriptomics, and experimental verification to elucidate and identify the effects and potential mechanisms of YSPDP against CKD.Methods: Firstly, we used metabolomics analyses to identify the chemical components of YSPDP.Then, network pharmacology was conducted and indicated the predicted signaling pathways regulated by YSPDP. Next, we conducted a 5/6 subtotal nephrectomy (5/6 SNx) rat model and treated these rats with YSPDP or Losartan for ten weeks to evaluate the effect of YSPDP on CKD.To further analyze the underlying mechanism of YSPDP in CKD, the kidney tissues of 5/6 SNx rats treated with vehicle and YSPDP were performed with transcriptome sequencing. Finally, the western blot was performed to validate the signaling pathways of YSPDP against CKD.Results: Twenty-four classes of chemicals were identified by metabolomics in YSPDP. YSPDP markedly hindered CKD progression, characterized by the restoration of body weight and serum albumin levels, improved renal function, diminished tissue injury, and hampered renal fibrosis in 5/6 SNx rats. The efficacy of YSPDP in ameliorating the progression of CKD was comparable to that of losartan. Furthermore, network pharmacology, transcriptomics, and functional enrichment analysis indicated the PI3K/AKT/mTOR signaling pathway was the key pathway regulated by YSPDP.Western blot validated the inhibition of PI3K/AKT/mTOR signaling in the kidney of 5/6 SNx rats treated by YSPDP.The study identified the chemicals of YSPDP and revealed that YSPDP prevented the progression of CKD by inhibiting PI3K/AKT/mTOR signaling in 5/6 SNx rats.

    Keywords: Network Pharmacology, Transcriptomics, 5/6 nephrectomy, PI3K/AKT/mTOR, Yishen Paidu Pills

    Received: 12 Oct 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Liu, Cao, Yuan, Xie, Zhu, Yao 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:
    Jun-li Yao, Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
    Chun Zhang, Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, 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.