Mechanism of Glycyrrhiza and glycyrrhetinic acid in cisplatin-induced acute kidney injury: a proteomics and metabolomics study
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.
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BibTeX
@article{tang2026mechanism,
title = {{Mechanism of Glycyrrhiza and glycyrrhetinic acid in cisplatin-induced acute kidney injury: a proteomics and metabolomics study}},
author = {Shanshan Tang and Xinbei Li and Fang Liao and Jian Zhang and Wanlin Yin and Xiaofeng Zheng and Haoyue Gao and Yi Deng and Xiaolong Lian and Yiying Wu and Qiong Man},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1776495},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1776495},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanism of Glycyrrhiza and glycyrrhetinic acid in cisplatin-induced acute kidney injury: a proteomics and metabolomics study
AU - Shanshan Tang
AU - Xinbei Li
AU - Fang Liao
AU - Jian Zhang
AU - Wanlin Yin
AU - Xiaofeng Zheng
AU - Haoyue Gao
AU - Yi Deng
AU - Xiaolong Lian
AU - Yiying Wu
AU - Qiong Man
PY - 2026
DA - 2026/11/05
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1776495
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1776495
AB - 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.
SN - 1663-9812
ER -