The Neuroprotective Effect Of Er-xian Decoction And Its Therapeutic Effect On Depression

Context: In clinical research,Erxian decoction(EXD)is used to treat perimenopausal syndrome in women.It is also used clinically to treat depression,but the mechanism remains unknown.Objectives: To investigate the neuroprotective effect of EXD,and its antidepressant potential.Methods: MTT assay,lactate dehydrogenase test,flow cytometry analysis,Hoechst staining,and western blotting were used to assess the apoptosis of PC12 cells.ICR mice were treated with EXD(0.5,1.5,and 4.5 g/kg i.g.)and fluoxetine(6.0 mg/kg i.g.)for 10 days.On day 10 of the treatment,depression-like behavior was induced by reserpine(2.5 mg/kg injected i.p.),and after 24 h of reserpine administration,it was assessed using the tail suspension and forced swimming tests.Apoptosis proteins and neurotransmitter were tested in vitro and in vivo,respectively.In addition,in a perimenopausal model of mice,female ICR mice were randomly divided into 6 groups:Low,medium and high dose of EXD groups(0.5,1.5,and 4.5 g/kg),soy isoflavones group(250 mg/kg)and control group.The mice in the control group received sham surgery(within ovaries),and the others were excised with bilateral ovaries and exerted by 28-day chronic mild unpredictable stimulation for the establishment of perimenopausal depression model.After 10 days of gavage,behavioral tests,H&E staining,western blotting and serum hormone levels were used to indicate the effect of EXD decoction on mice.Results: MTT assay results showed corticosterone prevented cell growth,but EXD at concentrations of 100,200,and 400 ?g/m L restored cell viability(EC50: 204.016?g/m L).EXD decreased lactate dehydrogenase leakage from 63.48 to 43.60 U/L,and upregulated expression of Bcl-2 while the expression of Bax,caspase-3,and caspase-8were decreased in vivo and in vitro.Moreover,EXD improved depression-like behavior in mice,and 4.5 g/kg EXD treatment increased the secretion of serotonin,dopamine,and norepinephrine by 67.44,28.12,and 42.12 pg/mg,respectively,in hypothalamus compared to that of reserpine group.In a perimenopausal model of mice,behavioral tests showed that EXD could relieve depression symptoms and improve spatial memory in mice.Western blotting showed that EXD significantly up-regulated the expression of BDNF and Bcl-2 in hippocampus and estrogen receptors(ERs)in the uterus and adrenals,protecting hippocampal tissue and antagonizing the symptoms of estrogen deficiency in mice,which was further proved within an uterine morphology test.In addition,EXD reduced the levels of follicle-stimulating hormone,luteinizing hormone and interleukin-6 in serum.Conclusions: EXD demonstrated neuroprotective effects and improved depression-like behavior in mice.Further research should be focused on the mechanism of the active components in EXD.