Antidepressant Effect And Underlying Mechanism Of Dihydromyricetin

Objective:This study investigated the effect and potential mechanisms on DHM-elicited antidepressant action.Methods:The antidepressant effect of DHM was validated via depression-related tail suspension test(TST)and forced swimming test(FST)in naive mice,as well as in the acute lipopolysaccharide-induced depression-like mice.The chronic unpredicted mild stress(CUMS)mouse model of depression was also used to assess the antidepressant-like effect of DHM by TST and FST,locomotor activity,and sucrose preference test(SPT).The protein levels of BDNF,ERK1/2-CREB-BDNF signaling pathway and inflammatory factors were determined through western blotting and enzyme-linked immunosorbent assay,respectively.Results:DHM reduced mice immobility time in the TST and FST.Similarly,DHM pretreatment also improved acute LPS-induced depression-like behaviors.Further,seven days of DHM treatment also ameliorated depression-related behaviors induced by CUMS,whereas similar treatment with the typical antidepressant venlafaxine did not.DHM activated the ERK1/2-CREB pathway and increased glycogen synthase kinase-3 beta(GSK-3?)phosphorylation at Ser-9,with upregulation of BDNF expression,in both hippocampal tissues and cultured primary hippocampal cells.Conclusion:The present data indicate that DHM exerts a more rapid antidepressant effect than that of a typical antidepressant venlafaxine.We further provided evidences that the antidepressant effect of DHM is likely associated with DHM-stimulate BDNF production and inhibition of neuroinflammation.