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 CUMS to induce depression model. The glutamate level in the hippocampus was determined by 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 chronic unpredictable mild stress (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-3 beta) inhibitor (10 mu M, 1( )mL). Among these treatments, the combination of Herba Rhodiolae and GSK-3 beta inhibitor was most effective. Abnormalities in the glutamate system and autophagy of the brain were decreased greatly in Herba Rhodiolae and GSK-3 beta 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-3 beta was remarkably suppressed by the GSK-3 beta inhibitor. Conclusions: These findings indicated that the combined effects of Herba Rhodiolae and GSK-3 beta inhibitor contributed to the activation of BDNFITrkB-GSK-3 beta signaling pathway.

Automated summary

The study showed that Herba Rhodiolae, venlafaxine, and a combination of Herba Rhodiolae and GSK-3 beta inhibitor were effective in alleviating depressive-like behaviors induced by chronic unpredictable mild stress in rats. The combination of Herba Rhodiolae and GSK-3 beta inhibitor showed the most significant effects in decreasing abnormalities in the glutamate system and autophagy of the brain, and promoting the BDNF/TrkB signaling pathway.