Baicalin exerts antidepressant effects through Akt/FOXG1 pathway promoting neuronal differentiation and survival

Background and aims: Impaired neurogenesis in hippocampus may contribute to a variety of neurological diseases, such as Alzheimer's disease and depression. Baicalin (BA), which is mainly isolated from the root Scutellaria baicalensis Georgi (traditional Chinese herb), which was reported to facilitate neurogenesis, but how to play the role and the underlying molecular mechanisms are still unknown. Main methods: In this study, we adopted the chronic unpredictable mild stress (CUMS)-induced mouse model of depression, and then explore antidepressant-like effects and possible molecular mechanisms. Key findings: We found that BA significantly increased sucrose consumption in sucrose preference test, the number of crossing in open filed test and attenuated immobility time in tail suspension test. Additionally, BA administration notably promoted neuronal differentiation and the number of DCX+ cells. Moreover, BA facilitated immature neurons develop into mature neurons and their survival. FOXG1, a transcription factor gene, which is crucial for mammalian telencephalon development, specifically stimulates dendrite elongation. BA could reverse the decrease of p-Akt, FOXG1 and FGF2 caused by CUMS-induced. Additionally, the expression of FOXG1 and FGF2 significantly decreased when the Akt pathway were inhibited by LY294002 in SH-SY5Y cells. Interestingly, BA failed to counteract the decline. Significance: These results suggest that BA could promote the differentiation of neurons, which transformation into mature neurons and their survival via the Akt/FOXG1 pathway to exert antidepressant effects.