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.

High‐mobility group box 1 emerges as a therapeutic target for asthma

“…HMGB1/TLR4/NF-κB, HMGB1/RAGE, JAK/STAT, and HMGB1/TGF-β play important roles in the occurrence and development of asthma. All of these pathways activate the HMGB1 to result in a range of inflammatory responses and damage of cells [90][91][92][93] (Figure 4). For example, HMGB1/RAGE signaling synergically enhances TGF-β1-induced broncho-airway remodeling and epithelial-mesenchymal transformation (EMT) by promoting Th17 cell differentiation and IL-17 secretion, which is one of the causes of severe steroid-resistant asthma.…”

Advanced Biomarkers of Hepatotoxicity in Psychiatry: A Narrative Review and Recommendations for New Psychoactive Substances

“…Another study in mice indicates that along with depressive behaviour, hippocampal and serum HMGB1 levels increased significantly after 4-week exposure to chronic unpredictable mild stress (CUMS) [123,124]. Sevoflurane was found to exert antidepressant effects by blocking the HMGB1/TLR4 pathway in CUMS-treated rats [125], and curcumin acts in a similar manner [126]. Arctiin also exhibits antidepressant effects by attenuating neuronal inflammation through the activation of NF-κB via the HMGB1/TLR4 and TNF-α/TNFR1 pathways [127].…”