Baicalin alleviates sepsis-associated acute kidney injury through activation of the PPAR-γ/UCP1 signaling pathway

Purpose This study aims to investigate the protective effect of baicalin on sepsis-associated acute kidney injury (SA-AKI) and its molecular mechanism.Materials and methods An SA-AKI mouse model was established via lipopolysaccharide (LPS) injection. Baicalin’s effects on renal function, oxidative s...

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Main Authors: Neng Bao, Ming-Jia Gu, Qiu-Ya Huang, Hai-Jian Sun, Xue-Xue Zhu, Xin Gu, Jin Wang, Xiang Yu, Qing-Bo Lu, Ya-Fen Yu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2508908
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Summary:Purpose This study aims to investigate the protective effect of baicalin on sepsis-associated acute kidney injury (SA-AKI) and its molecular mechanism.Materials and methods An SA-AKI mouse model was established via lipopolysaccharide (LPS) injection. Baicalin’s effects on renal function, oxidative stress, and apoptosis were evaluated using histopathology, dihydroethidium, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Bioinformatics, molecular docking, ribonucleic acid (RNA) sequencing, and Western blotting were employed to investigate the role of baicalin in regulating the peroxisome proliferator‑activated receptor‑γ (PPAR-γ)/uncoupling protein 1 (UCP1) pathway. Human kidney-2 cells were used for in vitro validation.Results In this study, baicalin significantly ameliorated LPS-induced acute kidney injury by modulating the PPAR-γ/UCP1 signaling pathway. Both in vivo and in vitro experiments revealed that baicalin attenuates inflammation, oxidative stress, and apoptosis while restoring mitochondrial function. RNA sequencing analysis revealed significant upregulation of PPAR-γ/UCP1 in the baicalin-treated group. Further molecular docking and molecular dynamics simulations confirmed a stable interaction between baicalin and UCP1. Validation via small interfering RNA-mediated knockdown of PPAR-γ and UCP1 revealed that inhibition of the PPAR-γ/UCP1 pathway abrogated baicalin’s protective effects, highlighting the critical role of this pathway in mediating baicalin’s renoprotection.Conclusion Baicalin protects against SA-AKI by activating the PPAR-γ/UCP1 signaling pathway. This study provides new insights into the mechanisms through which baicalin mitigates kidney injury in sepsis, suggesting its potential as a therapeutic agent for SA-AKI.
ISSN:0886-022X
1525-6049