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

TL;DR

Luteolin reduces depressive-like behaviors in stressed mice by blocking the JAK2/STAT3 pathway and reducing inflammation.

Contribution

This study is the first to show luteolin's antidepressant effects via the JAK2/STAT3 pathway and inflammation modulation in a mouse model.

Findings

Luteolin reduced phosphorylated JAK2 and STAT3 levels in CUMS-exposed mice.

Luteolin improved depressive-like behaviors in forced swim and sucrose preference tests.

Luteolin lowered pro-inflammatory cytokine levels caused by CUMS.

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.

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