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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1526465
This article is part of the Research Topic Crosstalk in Ferroptosis, Immunity & Inflammation View all 23 articles

Integrated UPLC-ESI-MS/MS, network pharmacology, and transcriptomics to reveal the material basis and mechanism of Schisandra chinensis Fruit Mixture against diabetic nephropathy

Provisionally accepted
Yuanyuan DENG Yuanyuan DENG *Xin-Yu Ma Xin-Yu Ma Pengfei He Pengfei He Mian-Zhi Zhang Mian-Zhi Zhang
  • Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China

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

    Backgrounds: It has been regarded as an essential treatment option for diabetic nephropathy (DN) in Traditional Chinese medicine. Previous studies have demonstrated the anti-DN efficacy of Schisandra chinensis Fruit Mixture (SM); however, a comprehensive chemical fingerprint is still uncertain, and its mechanism of action, especially the potential therapeutic targets of anti-DN, needs to be further elucidated.Objective: Potential mechanisms of SM action on DN were explored through network pharmacology and experimental validation.The chemical composition of SM was analyzed using UPLC-ESI-MS/MS technology.Active bioactive components and potential targets of SM were identified using TCMSP, SwissDrugDesign, and SymMap platforms. STZ induction. Hub targets and critical signalling pathways were detected using qPCR, Western blotting and immunofluorescence.Results: Utilizing the UPLC-ESI-MS/MS coupling technique, a comprehensive analysis identified 1281 chemical components of SM's ethanol extract, with 349 of these components recognized as potential bioactive compounds through network pharmacology. Through this analysis, 126 shared targets and 15 HUB targets were pinpointed. Of these, JAK2 is regarded as the most critical gene. Enrichment analysis revealed that SM primarily operates within the PI3K/AKT signaling pathway. In vivo experiments confirmed that SM improved pathological injury and renal function in rats with DN while improving mitochondrial morphology and function and modulating the expression of proteins linked to apoptosis (cleaved-caspase-3, Bax, and Bcl-2) and pro-inflammatory factors (IL-6 and TNF-α). Mechanistically, SM alleviates DN primarily by suppressing the PI3K/AKT/mTOR and JAK2/STAT3 signaling pathways to fulfill the energy needs of renal tissues. Furthermore, molecular docking analysis provided direct validation of these findings.The findings of this study offer initial indications of the active component and robust anti-inflammatory and anti-apoptotic characteristics of SM in the mitigation of DN, along with its capacity to safeguard the integrity and functionality of mitochondria. This research unequivocally validates the favorable anti-DN effects of SM, indicating its potential as a viable pharmaceutical agent for the management of DN.

    Keywords: Network Pharmacology, diabetic nephropathy, Schisandra chinensis fruit Mixture, AKT, protein kinase B, AUC, area under the curve, ACEi, angiotensinconverting enzyme inhibitors, ARBs, angiotensin receptor blockers, Bcl-2, B-cell lymphoma-2

    Received: 11 Nov 2024; Accepted: 26 Dec 2024.

    Copyright: © 2024 DENG, Ma, He 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: Yuanyuan DENG, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 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.