(−)‐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.