Curcumin Ameliorates Chronic Mild Stress-Induced Depressive-Like Behavior via HMGB1/TLR4/NF-κB Signaling Pathway

Abstract BackgroundDepression, one of the most frequently-occurring psychiatric disorders worldwide, is a significant inflammatory disorder. The polyphenol curcumin (Cur), which is extracted from Curcuma longa, has marked anti-inflammatory and anti‑oxidative effects against inflammatory diseases. However, whether Cur has antidepressant effects and the possible mechanisms, are unclear. The present study aimed to assess Cur’s beneficial effects on depressive-like behaviors using a chronic unpredictable mild stress (CUMS) model and its possible molecular mechanisms. MethodsWe performed CUMS treated Sprague Dawley (SD) rats as a model of depression. Behavioral observations were performed by sucrose preference test (SPT), force swimming test (FST) and tail suspension test (TST). Hippocampal expression of oxidative stress markers and inflammatory cytokines were measured with ELISA. Hippocampal expression of high-mobility group box 1 (HMGB1), IL-1β, TNF-α and IL-6 were determined with quantitative PCR analyses and immunofluorescent staining. Hippocampal Toll-like receptor 4 (TLR4) and NF-κB activation were examined with Western blotting analysis.ResultsRats subjected to CUMS demonstrated marked depressive-like behavior (decreased locomotor activity and sucrose intake, and prolonged immobility). Their levels of oxidative stress and inflammatory cytokines increased significantly, and their levels of phosphorylated nuclear factor kappa-B (NF-κB), toll-like receptor 4 (TLR4), and HMGB1, also increased in the hippocampus. The changes were ameliorated significantly by treatment with Cur (50, 100 mg/kg) to varying degrees.Conclusion This study demonstrated that Cur has a potent antidepressant effect via the HMGB1/TLR4/NF-κB pathway, suggesting that Cur might be a promising therapeutic drug for depression.