Abstract
Background: Studies have reported that depression is associated with increased level of oxidative stress and accompanied with decreased Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1-nuclear factor (erythroid-derived 2)-like 2 (Keap1-Nrf2) signaling pathway. Berberine has been shown to possess properties on protection against neurodegenerative diseases, but its effects on chronic unpredictable mild stress (CUMS) induced depressive such as behaviors and Keap1-Nrf2 signaling pathway are unknown. Objective: This study was designed to evaluate the effect of berberine on CUMS induced depression animal model and investigate the underlying mechanisms. Materials and Methods: We established CUMS depressant rats model and treated CUMS rats with berberine. Sucrose preference test, forced swim test , and tail suspension test were used to measure behavioral changes. We used quantitative polymerase chain reaction and western blot to test the levels of cytokines in the hippocampus. Results: We found that CUMS rats displayed obvious depressive-like behaviors. Moreover, berberine treatment prevented depressive behaviors in CUMS rats accompanied with suppression of oxidative stress markers. Further experiments showed that berberine treatment up-regulated the expression of Keap1-Nrf2 antioxidant signaling pathway and its downstream neuroprotective factors. Conclusion: The present results suggested that treatment of berberine significantly ameliorated depressive-like behaviors in CUMS rats and enhanced Keap1-Nrf2 antioxidant signaling pathways in hippocampus. Abbreviations used: MDD: Major depressive disorder; CUMS: Chronic unpredictable mild stress; FST: Forced swim test; TST: Tail suspension test; Keap1: Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1; Nrf2: nuclear factor (erythroid-derived 2)-like 2; ARE: Antioxidant response elements; SOD: Superoxide Dismutase; MDA: Malonic dialdehyde; IMI: Imipramine.
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