{
  "abstract": "BackgroundAcute kidney injury (AKI) is a frequent and serious complication associated with cisplatin (CP), severely limiting its clinical use. Glycyrrhiza (GL) has been clinically used in China for detoxification, and its primary active ingredient, Glycyrrhetinic acid (GA), demonstrates detoxification effects. Studies conducted previously have shown that GL and GA offer protection against CP-induced AKI. However, the precise mechanism underlying this effect is unclear.PurposeThe mechanisms of GL and GA in alleviating CP-induced AKI were investigated using proteomics and metabolomics.MethodsA rat model of CP-induced AKI was established. Proteomics using DDA-PASEF-based label-free LC-MS/MS and metabolomics using UPLC-Q-TOF MS were employed to detect differentially expressed proteins (DEPs) and metabolites (DEMs) in renal tissues and plasma. A protein-protein interaction network between disease targets and DEPs was constructed, correlation analysis and pathway enrichment were employed to uncover the protective mechanisms. To confirm the mechanisms, the primary proteins involved in the above processes were identified using Western blot, immunohistochemistry, and enzyme-linked immunosorbent assay.ResultsThe interventions alleviated CP-induced AKI, reduced serum BUN and Cr levels and alleviated histopathological renal injury. Proteomics results indicated the participation of GL and GA in biological processes such as complement activation, acute-phase response and inflammatory response by regulating related DEPs. Metabolomics results suggested that DEMs related to lipid, energy, and amino acid metabolism were regulated to alleviate metabolic disorders in kidney injury. GL participated in the multiple pathways related to inflammatory response and apoptosis, and showed an interplay with Agt, Stat2, Vtn, Plg, Cyp2e1, C7, Cfd, and Serping1. GA was found to participate in above pathways via the regulation of DEPs strongly correlated with AKI effector molecules and exhibited a strong interplay with Hspb1, Crp, Cfh, Slc12a1, Vtn, Kng1, and Cdc37. The intervention led to a reversal in the expression of primary proteins involved in these processes, consistent with proteomics findings.ConclusionGL and GA mitigate cisplatin-induced kidney damage through various mechanisms, including the coordinated changes in inflammatory and acute-phase responses, survival/apoptosis-related proteins, and energy, lipid, and amino acid metabolism. These findings identify several candidate molecular networks associated with the renoprotective effects of GL and GA and provide a basis for further mechanistic investigation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "Shanshan Tang"
    },
    {
      "name": "Xinbei Li"
    },
    {
      "name": "Fang Liao"
    },
    {
      "name": "Jian Zhang"
    },
    {
      "name": "Wanlin Yin"
    },
    {
      "name": "Xiaofeng Zheng"
    },
    {
      "name": "Haoyue Gao"
    },
    {
      "name": "Yi Deng"
    },
    {
      "name": "Xiaolong Lian"
    },
    {
      "name": "Yiying Wu"
    },
    {
      "name": "Qiong Man"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fxvynmqbrk0be.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1776495",
  "fulltext_url": null,
  "id": "fxvynmqbrk0be",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1776495",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fxvynmqbrk0be.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:15Z",
      "native_id": "10.3389/fphar.2026.1776495",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1776495"
    },
    {
      "first_seen": "2026-11-05T12:21:25Z",
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      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1776495/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Mechanism of Glycyrrhiza and glycyrrhetinic acid in cisplatin-induced acute kidney injury: a proteomics and metabolomics study",
  "title_text": "Mechanism of Glycyrrhiza and glycyrrhetinic acid in cisplatin-induced acute kidney injury: a proteomics and metabolomics study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T00:21:24Z",
  "url": "https://research.draconitic.com/paper/fxvynmqbrk0be",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}