The protective effects of Mogroside V and its metabolite 11-oxo-mogrol of intestinal microbiota against MK801-induced neuronal damages

• Published in: Psychopharmacology 2020-04, Vol.237 (4), p.1011-1026
• Main Authors: Ju, Peijun, Ding, Wenhua, Chen, Jianhua, Cheng, Ying, Yang, Beibei, Huang, Lanting, Zhou, Qiong, Zhu, Cuizhen, Li, Xiaobo, Wang, Mengyue, Chen, Jinghong
• Format: Article
• Language: English
• Subjects: Adult; AKT protein; Animal models; Animals; Apoptosis; Axonogenesis; Biomedical and Life Sciences; Biomedicine; Calcium; Calcium (intracellular); Cell culture; Dizocilpine; Dizocilpine Maleate - toxicity; Excitatory Amino Acid Antagonists - toxicity; Female; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - physiology; Glutamic acid receptors (ionotropic); Health aspects; Humans; Inflammation; Intestinal microflora; Intestine; Male; Mental disorders; Metabolites; Mice; Mice, Inbred C57BL; Microbiota; Microbiota (Symbiotic organisms); Middle Aged; N-Methyl-D-aspartic acid receptors; Neurons; Neurons - drug effects; Neurons - pathology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Original Investigation; Pharmacology/Toxicology; Phosphorylation; Plant protection; Plants; Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - pathology; Psychiatry; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Schizophrenia; Schizophrenia - chemically induced; Schizophrenia - pathology; Schizophrenia - prevention & control; Sweetening Agents - pharmacology; Sweetening Agents - therapeutic use; TOR protein; Triterpenes - pharmacology; Triterpenes - therapeutic use; Young Adult
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-019-05431-9

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 [Ca 2+ ] 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.