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PLoS ONE

PLoS ONE

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Luteolin alleviates CUMS-induced depressive-like behavioral deficits in mice through blocking the JAK2/STAT3 pathway

Published:24 October 2025 DOI: 10.1371/journal.pone.0335057 PMID: 41134796
Hai-Hong Wu,?Shang-Yue Chen,?Dong-Liang Yuan,?Ting Zhao

Abstract

This study probed into the potential effects of luteolin (LUT) on depressive-like behavioral deficits caused by chronic unpredictable mild stress (CUMS) in mice, with a focus on its underlying molecular mechanisms. Western blot analysis revealed that CUMS notably activated the JAK2/STAT3 pathway, as indicated by elevated levels of phosphorylated JAK2 (p-JAK2) and p-STAT3. Treatment with LUT notably diminished p-JAK2 and p-STAT3, suggesting that LUT alleviates CUMS-induced depressive-like behavioral deficits by blocking the JAK2/STAT3 pathway. Behavioral assessments, including the forced swim and sucrose preference tests, demonstrated that LUT remarkably improved depressive-like symptoms. Furthermore, LUT treatment diminished the levels of pro-inflammatory cytokines, which were elevated by CUMS, further supporting the involvement of LUT in exerting antidepressant activities via the modulation of inflammatory responses. This study is the first to integrate multidimensional evidence from behavioral tests, neuroinflammation, and the JAK2/STAT3 signaling pathway, systematically demonstrating that luteolin alleviates CUMS-induced depression-anxiety comorbidity through synergistic regulation of an antioxidant?anti-inflammatory?neural signaling network.

Substances (12)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Luteolin 491-70-3 C15H10O6 754 suppliers $5.00-$1595.00
Luteolin 491-70-3 C15H10O6 754 suppliers $5.00-$1595.00
Luteolin 491-70-3 C15H10O6 754 suppliers $5.00-$1595.00
Luteolin 491-70-3 C15H10O6 754 suppliers $5.00-$1595.00
Luteolin 491-70-3 - Inquiry
Luteolin 491-70-3 - Inquiry
Luteolin 491-70-3 - Inquiry
Luteolin 491-70-3 - Inquiry
Luteolin 491-70-3 - Inquiry
Luteolin 491-70-3 - Inquiry

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