Berberine Ameliorates Chronic Unpredictable Mild Stress Induced Depression Like Behaviors and Elevating Kelch-like Erythroid Cell-derived Protein with CNC Homology-associated Protein 1-nuclear Factor (Erythroid-derived 2)-like 2 Antioxidant Signaling Pathways

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.