Peijun Ju1,2, Wenhua Ding1,3, Jianhua Chen1, Ying Cheng1, Beibei Yang1, Lanting Huang1, Qiong Zhou1, Cuizhen Zhu1,4, Xiaobo Li1, Mengyue Wang5, Jinghong Chen6,7. 1. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 201108, China. 2. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 3. The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangdong, Guangzhou, China. 4. Anhui Mental Health Center, Hefei, Anhui Province, China. 5. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 201108, China. mywang@sjtu.edu.cn. 6. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 201108, China. chenjh_008@hotmail.com. 7. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. chenjh_008@hotmail.com.
Abstract
RATIONALE: Animal models, notably with non-competitive NMDA receptor antagonist MK801, are commonly used to investigate the mechanisms of schizophrenia and to pursue its mechanism-related drug discoveries. OBJECTIVES: In the current study, we have extensively examined the protective effects of MogrosideV (MogV), a plant-derived three terpene glucoside known to exhibit anti-oxidative and anti-inflammatory activities. METHODS AND RESULTS: Here, we investigated its protective effects against neuronal damages elicited by MK-801 treatment. Our behavioral experimental results showed that MK-801-induced PPI deficits and social withdrawal were prevented by MogV treatment. Moreover, the cellular and neurochemical responses of MK-801 in medial prefrontal cortical cortex (mPFC) were also ameliorated by MogV treatment. Also, profiling metabolites assay through artificial intestinal microbiota was performed to identify bioactive components of MogV. An in vitro study of primary neuronal culture demonstrated that MogV and its metabolite 11-oxo-mogrol treatment prevented the MK-801-induced neuronal damages through the mechanisms of promoting neurite outgrowth, inhibiting cell apoptosis, and [Ca2+]i release. Additionally, 11-oxo-mogrol reversed inactivation of phosphorylation levels of AKT and mTOR induced by MK801. CONCLUSIONS: These results suggest therapeutic potential of MogV for schizophrenia.
RATIONALE: Animal models, notably with non-competitive NMDA receptor antagonist MK801, are commonly used to investigate the mechanisms of schizophrenia and to pursue its mechanism-related drug discoveries. OBJECTIVES: In the current study, we have extensively examined the protective effects of MogrosideV (MogV), a plant-derived three terpene glucoside known to exhibit anti-oxidative and anti-inflammatory activities. METHODS AND RESULTS: Here, we investigated its protective effects against neuronal damages elicited by MK-801 treatment. Our behavioral experimental results showed that MK-801-induced PPI deficits and social withdrawal were prevented by MogV treatment. Moreover, the cellular and neurochemical responses of MK-801 in medial prefrontal cortical cortex (mPFC) were also ameliorated by MogV treatment. Also, profiling metabolites assay through artificial intestinal microbiota was performed to identify bioactive components of MogV. An in vitro study of primary neuronal culture demonstrated that MogV and its metabolite 11-oxo-mogrol treatment prevented the MK-801-induced neuronal damages through the mechanisms of promoting neurite outgrowth, inhibiting cell apoptosis, and [Ca2+]i release. Additionally, 11-oxo-mogrol reversed inactivation of phosphorylation levels of AKT and mTOR induced by MK801. CONCLUSIONS: These results suggest therapeutic potential of MogV for schizophrenia.
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