(-)-Epigallocatechin Gallate Ameliorates Chronic Stress-Induced Depression-Like Behavior in Rats by Inhibiting the NF-κB/Caspase-1 Signaling Pathway and Reducing IL-1β and IL-18 Expression.

This study aimed to further clarify the ameliorative effects of epigallocatechin-3-gallate (EGCG) on depression and depression-like behaviors induced by chronic unpredictable mild stress (CUMS) in female Sprague-Dawley (SD) rats. EGCG was administered via intraperitoneal injection, and liver function and blood lipid profiles were assessed. Western blot analysis was employed to determine the expression levels of caspase-1 and nuclear factor kappa B (NF-κB), as well as inflammatory factors interleukin-1β (IL-1β) and interleukin-18 (IL-18). The results showed that CUMS induced depression-like behaviors (including anhedonia and behavioral despair) in rats, accompanied by reduced body weight, decreased liver index, and dyslipidemia. Western blot analysis revealed significantly elevated expression of pyroptosis-related proteins (NF-κB, cleaved-caspase-1, IL-1β, and IL-18) in both the liver and brain tissues of the CUMS group. EGCG treatment could reverse these results. Notably, female rats exhibited more severe CUMS-induced depression-like behaviors than male rats. These findings suggest that EGCG can alleviate CUMS-induced depression-like behaviors (anhedonia and behavioral despair) in female rats. This protective effect may be mediated by inhibiting the NF-κB/caspase-1 pyroptosis pathway, reducing IL-1β and IL-18 expression, thereby improving hepatocellular pyroptosis and alleviating liver injury.