Meihua Wang1,2, Lei Yang1, Zhilin Chen3, Linlu Dai4, Caihua Xi1, Xing Wu1, Gang Wu1, Yang Wang5, Jin Hu6. 1. Department of Neurosurgery & Neurocritical Care, Huashan Hospital Affiliated To Fudan University, 958 Jinguang Road, Minhang District, Shanghai, 200040, China. 2. Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China. 3. Department of Neurology, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200081, China. 4. Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China. 5. Department of Emergency, Xinhua Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. wang1989727@126.com. 6. Department of Neurosurgery & Neurocritical Care, Huashan Hospital Affiliated To Fudan University, 958 Jinguang Road, Minhang District, Shanghai, 200040, China. hujin_dana@126.com.
Abstract
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.
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 depressionmice. 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.