Neuroprotective Effects Of Loganin On MPTP-induced Parkinson's Disease Mouse Model

Parkinson's disease(PD)is the second major neurodegenerative diseases secondarily to Alzheimer's disease.Its main clinical manifestation is resting tremor,bradykinesia,and other behavior disorders.The mechanism of PD are mainly involved in environment,genetic deficiency,aging,and other potential mechanisms such as inflammation,oxidative stress,endoplasmic reticulum stress,autophagy,etc.However,the treatment of Parkinson's disease is under slow development.At present,researches of potential drugs are still not enough and there are still a lot of potential monomers needed for development,including natural monomers.Loganin(Log)is a natural product extracted from the fruits of cornus(Cornus officinalis Sieb.et Zucc.).Previous study report that loganin shows protective effects by regulating immunoreactivity on rats,alleviating oxidative stress injury induced by H2O2 to promote cell survival,improving spatial memory in diabetic rats.These data from cell lines and animal experiments indicate potential neuroprotective roles of loganin.Here,we attempt to determine whether loganin shows neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse model.We performed loganin on MPTP-induced PD mouse model with pre-treatment and post-treatment,and evaluated the effect of loganin with various aspects as the follows: locomotor activity by a pole test,concentration of dopamine and 3,4-dihydroxyphenylacetic acid(DOPAC)in striatum with high performance liquid chromatography(HPLC),expression of tyrosine hydroxylase(TH),inflammatory cytokines such as caspase-3 and TNF-?,and upstream molecules of NF?B,p38,c-Abl,LC3-II,Drp1 in striatum by Western blot and ELISA,glia activation in substantia nigra(SN),caspase-3,c-Abl,LC3-II in SN.Cell experiment was applied for staining with acridine orange to detect acidic vesicular organelles(AVOs).We found out that dopamine level and tyrosine hydroxylase expression were significantly higher in striatum of mice with post-treatment of loganin than MPTP model,as well as shortening total locomotor activity(TLA)time,while pre-treatment showed no effect.There is no difference on DOPAC level between groups.The number of dopaminergic neurons in the substantia nigra of PD mice increased in loganin post-treatment group.The number of activated microglia and astrocytes decreased following loganin post-treatment.Expression of caspase-3,TNF-? and their upstream molecules like NF?B,p38 and c-Abl also decreased following loganin post-treatment,as well as the expression of LC3-II and Drp1.Cell experiment displayed alleviation of AVOs with pre-treatment and post-treatment of loganin.We conclude that loganin shows neuroprotective effects by inhibiting inflammation and a c-Abl-p38-NF?B pathway,and has effects on autophagy.Loganin exerts neuroprotective effects PD and could serve as a therapeutic drug to ameliorate PD.