Depression is a disease that seriously threatens the quality of human life. To explore the effect of gentiopicroside on depression, this study investigated the therapeutic effect of gentiopicroside on corticosterone-induced depressionin vivo and in vitro by using metabolomic methods.

A total of 36 rats were randomly assigned to three groups: a normal group, model group (depression), and treatment group (depression + gentiopicroside). Corticosterone was administrated to induce depression-like model rats. Morris water maze test was used to validated the behavior performance. The hippocampus of rats was obtained for metabolomic detection. Metabolites that were differentially expressed between the groups were extracted for Heatmap, Go, and pathway enrichment analyses. Finally, neuronal cells were cultured and examined to validated the effect of gentiopicroside.

Corticosterone injured rats learning capacity, and decreased the levels of 5-HT, and reversed by gentiopicroside delivery. Metabolites obtained from the hippocampus of rats in the three groups were subjected to a principal component analysis (PCA). Go and pathway enrichment analyses revealed the involvement of sphingolipid metabolism et al. Gentiopicroside could inhibit apoptosis caused by corticosterone, and also decrease neuronal cell proliferation and BDNF levels in vitro. Arachidonic acid (ARA) reversed the protective effect of gentiopicroside on neuronal cells.

These findings suggest that gentiopicroside reduces apoptosis and increases the proliferation of hippocampus cells in depressed animals by regulating metabolites. Moreover, our study provides a new basis for the clinical treatment of depression and demonstrates the potential efficacy of gentiopicroside in this area of pathology.