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 GSK3β. 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/GSK3β signaling, reduced the level of ceramide and hippocampal neuron apoptosis.

中文翻译：

---

栀子苷通过 PI3K/Akt/GSK3β 轴抑制神经酰胺-PP2A 信号传导，改善慢性不可预测的轻度应激诱导的抑郁样行为

背景

抑郁症是一种严重的精神障碍。不幸的是，超过一半的重度抑郁症患者在使用抗抑郁药初始治疗后无法缓解。栀子苷是一种从栀子花中分离出的生物活性环烯醚萜苷，可以改善小鼠的抑郁样行为。但是，其底层机制还不是很清楚。

方法

使用ELISA、免疫荧光和Western blot等药理方法研究栀子苷对慢性不可预测轻度应激(CUMS)诱导的抑郁小鼠的作用。

结果

在这项研究中，我们发现栀子苷可以抑制 CUMS 诱导的小鼠抑郁样行为。栀子苷能降低海马神经酰胺水平，降低酸性鞘磷脂酶（ASM）的活性；此外，ASM抑制剂（阿米替林）可以降低神经酰胺的浓度，改善小鼠的抑郁样行为。此外，栀子苷还可以减轻 CUMS 诱导的海马神经元凋亡，并增加 PI3K、Akt 和 GSK3β 的磷酸化形式。此外，PI3K 抑制剂 (LY294002) 还可在体外消除栀子苷对海马神经元的神经保护作用。

结论

这些结果表明栀子苷对 CUMS 小鼠具有潜在的抗抑郁样作用，其作用可能与激活的 PI3K/Akt/GSK3β 信号、降低神经酰胺水平和海马神经元凋亡有关。