Neuroprotective Effect And Mechanism Of Mogrosides On Parkinson's Disease Model Mice

Parkinson’s disease(PD)is the second largest neurodegenerative disease in the world,which is common in the middle-aged and elderly.Its clinical manifestations are mainly motor retardation,muscle stiffness and resting tremor,as well as non-motor symptoms such as anxiety,depression and cognitive impairment.The main pathological feature is the degeneration and loss of dopaminergic neurons in the substantia nigra of the brain.The etiology of PD is complex,involving not only genetic factors,but also environmental factors,but its pathogenesis is still unclear.PD will lead to a serious decline in the quality of life,causing a great burden on individual patients and society.However,there is no specific drug for the treatment of PD in clinic.It is of high medical value and social significance to seek new drugs that can effectively prevent or treat PD and explore new mechanisms of anti-PD.Swingle is a traditional medicine and food homologous plant in ethnic minority areas of China.Mogrosides have been considered as a good sweetener and have effects on anti-diabetes and anti-cancer.In recent years,studies have shown that mogrosides and its metabolites effectively protect neurons from MK801-induced neuronal damage,which is considered as a potential drug for the treatment of schizophrenia,and mogrol has been found to significantly reduce dementia-like behavior in Alzheimer’s disease model mice.However,the effect of mogrosides on PD has not been studied.In this paper,the effect and mechanism of mogrosides in Parkinson’s disease model mice were studied by in vitro experiment,in vivo experiment and metabonomic analysis.Firstly,we established the PD model of SY5Y cells induced by MPP+.After adding mogroside Ⅴ and mogrol,we found that they could significantly improve the damage of SY5Y cells induced by MPP+and protect neurons.Secondly,we carried out the in vivo experiment.Through the establishment of MPTP-induced PD model mice and intraperitoneal injection of mogroside Ⅴ and mogrol,it was found that mogrosides could effectively improve the behavioral changes and brain pathological changes of PD mice,and had a significant protective effect on neurons in the substantia nigra of PD mice.Finally,in order to further explore the neuroprotective mechanism of mogrosides,we examined the metabonomics in the substantia nigra of mice.The results showed that the differential metabolites recovered significantly after administration were dihydro-D-sphingosine,N-acetyl-L-glutamic acid,trimethylamine N-oxide,hexadecanoic acid,9-octadecenal and 1,11-undecane dicarboxylic acid.The metabolic pathway mainly focuses on lipid,sphingolipid metabolism and amino acid synthesis.The analysis shows that mogrosides protect neurons mainly by regulating amino acid synthesis,lipid metabolism and gut-brain axis homeostasis.In conclusion,this paper explored the neuroprotective effect of mogrosides on Parkinson’s model mice and its mechanism.It was proved that mogroside Ⅴ,and mogrol had neuroprotective effects on PD from both in vitro and in vivo experiments.The results of metabonomic analysis show that they play a neuroprotective role by regulating brain homeostasis in PD mice by balancing amino acid synthesis,lipid metabolism and gastrointestinal metabolites,thereby reducing mitochondrial dysfunction and loss of neurons in the substantia nigra.