摘要
Background:Stressful life experiences are associated with neurobehavioral abnormalities,such as anxiogenic-related depression and cognitive decline.Reportedly,adaptogens are well known to modulate stress-related re-sponses and promote resilience.Objective:This study aimed to assess the potential mechanisms and adaptogenic properties of diosgenin(DG),a phytosteroidal sapogenin with neuroendocrine protective effects,in chronic unpredictable mild stress(CUMS)-induced anxiogenic-depression and cognitive deficits in mice.Methods:During the 21-day study,mice were divided into five groups,and were daily treated with 5%dimethyl sulfoxide(control and CUMS model),diosgenin(25 mg/kg and 50 mg/kg)or fluoxetine(10 mg/kg)orally,re-spectively,followed by 21-item CUMS paradigm exposure,except for the control group.Mice were examined for anxiety,depression and cognitive-like features using relevant neurobehavioral paradigms.Biomarkers of ox-idative stress,nitrite level,pro-inflammatory cytokines(TNF-𝛼,IL-6),acetylcholinesterase(AChE),glutamic acid decarboxylase(GAD),and monoamine oxidase-B(MAOB)were measured in the prefrontal cortex,striatum,and hippocampal regions of the brain.Also,adrenal hypertrophy,serum corticosterone and glucose levels as a mea-sure of hypothalamic pituitary adrenal(HPA)axis involvement were examined.Results:DG ameliorated CUMS-induced behavioral anomaly,as characterized by the increased duration of groom-ing bouts in the sucrose preference test;decreased duration of immobility in the tail suspension and forced swim tests;anxiolytic effects in the elevated-plus maze,hole-board,light/dark compartment tests,as well as cognitive impairments indexed by the Y-maze and object recognition tests were reversed by DG respectively.DG remarkably decreased adrenal hypertrophy and elevated serum levels of corticosterone and glucose in CUMS mice.Conclusion:Conclusively,DG exhibits antidepressant-like and anxiolytic-like actions with memory enhancement in the CUMS mouse model,and thus could serve as an alternative agent
