Journal
PSYCHOPHARMACOLOGY
Volume 238, Issue 10, Pages 2789-2800Publisher
SPRINGER
DOI: 10.1007/s00213-021-05895-8
Keywords
Geniposide; Depression; Chronic unpredictable mild stress; Ceramide; Acid sphingomyelinase; PI3K/Akt/GSK3 beta signaling
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Funding
- Biomedical and Engineering cross youth fund of Shanghai Jiao Tong University [YG2021QN43]
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Geniposide has shown to inhibit depressive-like behaviors induced by chronic unpredictable mild stress (CUMS) in mice, possibly through activation of the PI3K/Akt/GSK3 beta signaling pathway, reducing ceramide levels, and preventing hippocampal neuronal apoptosis.
Background Depression is a severe mental disorder. Unfortunately, more than half of patients with major depression disorder cannot achieve remission after initial treatment with an antidepressant. Geniposide, a bioactive iridoid glycoside isolated from Gardenia jasminoides Ellis, can ameliorate depressive-like behaviors in mice. However, the underlying mechanism is still not very clear. Methods The pharmacological methods including ELISA, immunofluorescence, and Western blot were used to investigate the role of geniposide on chronic unpredictable mild stress (CUMS)-induced depression mice. Results In this study, we found that geniposide could inhibit CUMS-induced depressive-like behaviors in mice. Geniposide is able to reduce the levels of ceramide and lower the activity of acid sphingomyelinase (ASM) in hippocampus; besides, ASM inhibitor (amitriptyline) can decrease the concentration of ceramide and ameliorate depressive-like behaviors of mice. Moreover, geniposide can also alleviate CUMS-induced hippocampal neuronal apoptosis and increase the phosphorylated form of PI3K, Akt, and GSK3 beta. Additionally, PI3K inhibitor (LY294002) can also abolish the neuroprotective effect of geniposide on hippocampal neurons in vitro. Conclusions These results indicate that geniposide exert a potential antidepressant-like effect on CUMS mice, and its effect might be associated with activated PI3K/Akt/GSK3 beta signaling, reduced the level of ceramide and hippocampal neuron apoptosis.
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