[Investigation on antidepressant mechanism of Piper laetispicum extract based on quantitative proteomics and zebrafish model of depression induced by chronic unpredictable mild stress].

This study aimed to evaluate the antidepressant activity of Piper laetispicum extract and preliminarily explore its underlying mechanism using a zebrafish model of depression combined with quantitative proteomics. A chronic unpredictable mild stress(CUMS) paradigm was employed to establish the depression model. AB strain zebrafish were randomly assigned into four groups: control, model, P. laetispicum, and fluoxetine, with 15 fish in each group. Except the control group, all groups were subjected to CUMS for 2 weeks. Intervention of P. laetispicum extract or fluoxetine lasted for 3 consecutive weeks. Upon completion of the experiment, the pathological morphology of zebrafish brain tissue was observed, and the expression levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), brain-derived neurotrophic factor(BDNF), and 5-hydroxytryptamine receptor 2A(5-HT2A) were measured in each group. Brain tissue proteins were extracted and subjected to quantitative proteomic analysis to identify differentially expressed proteins(DEPs), which was followed by bioinformatics analysis. Key DEPs were validated using Western blot and RT-qPCR. The results demonstrated that P. laetispicum extract significantly ameliorated CUMS-induced brain histopathological damage, reduced the levels of the inflammatory cytokines TNF-α and IL-1β, and reversed the aberrant expression of BDNF and 5-HT2A. Proteomic profiling identified a total of 11 633 proteins, among which the expression levels of 81 proteins were markedly reversed following P. laetispicum extract treatment. Subsequent validation by Western blot and RT-qPCR confirmed that P. laetispicum significantly modulated the expression of annexin A1(Anxa1) and transcription factor JunB(JunB). Collectively, these findings suggest that P. laetispicum exerts antidepressant effects potentially through the regulation of Anxa1 and JunB expression.