Herba Rhodiolae alleviates depression via the BDNF/TrkB-GSK-3β signaling pathway

BACKGROUND: Depression is one of the most common psychiatric disorders worldwide. Many antidepressant drugs are only effective for specific patients and their long-term use can lead to treatment resistance. There is an ongoing need for more effective antidepressant treatments. METHODS: The rats were exposed to chronic unpredictable mild stress (CUMS) to induce depression model. The glutamate level in the hippocampus was determined by high performance liquid chromatography (HPLC). Protein levels in the tissues were measured using western blotting. The fluid consumption test was performed to evaluate potential anhedonia. Open field test was conducted to evaluate locomotor activity. Forced swimming test was used to evaluate susceptibility to negative mood. RESULTS: In the present study, the depressive-like behaviors induced by CUMS were alleviated in rats by treatments with Herba Rhodiolae (0.04 g/kg, 1 mL), venlafaxine (0.035 g/kg, 1 mL), and combination of Herba Rhodiolae and glycogen synthase kinase 3 beta (GSK-3β) inhibitor (10 µM, 1 mL). Among these treatments, the combination of Herba Rhodiolae and GSK-3β inhibitor was most effective. Abnormalities in the glutamate system and autophagy of the brain were decreased greatly in Herba Rhodiolae and GSK-3β inhibitor-treated CUMS rats. Herba Rhodiolae was more effective in promoting the brain derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The expression of GSK-3β was remarkably suppressed by the GSK-3β inhibitor. CONCLUSIONS: These findings indicated that the combined effects of Herba Rhodiolae and GSK-3β inhibitor contributed to the activation of BDNF/TrkB-GSK-3β signaling pathway.