Study On Neuroprotective Activity And Mechanism Of Evodiamine Against Alzheimer's Disease

Evodiamine(Evo),a major alkaloid compound isolated from the dry unripened fruit of Evodia fructus,has a wide range of pharmacological activities.The present study sought to explore the neuroprotective effects of Evo in L-glutamate(L-Glu)-induced apoptosis of HT22 cells,and in a D-galactose and aluminum trichloride-developed Alzheimer's disease(AD)mouse model.Evo significantly enhanced cell viability,inhibited the accumulation of reactive oxygen species,ameliorated mitochondrial function,increased the B-cell lymphoma-2 protein content,and inhibited the high expression levels of Bax,Bad,and cleaved-caspase-3 and-8 in L-Glu-induced HT22 cells.Evo also enhanced the phosphorylation activities of protein kinase B and the mammalian target of rapamycin in the L-Glu-induced HT22 cells.In the AD mouse model,Evo reduced the aimless and chaotic movements,reduced the time spent in the central area in the open field test,and decreased the escape latency time in the Morris water maze test,increased the step-down latency time in the step-down test and improved endurance times in rotarod test.Evo reduced the deposition of amyloid beta 42(A?42)in the brain,and increased the serum level of A?42,but showed no significant effects on A?40.In addition,6 weeks of Evo administration significantly suppressed oxidative stress by modulating the related enzyme levels.In the central cholinergic system of AD mice,Evo significantly increased the serum levels of acetylcholine and choline acetyltransferase and decreased the level of acetylcholinesterase in the serum,hypothalamus,and brain.Meanwhile,Evo can also increase the expression of P-Akt and P-mtor,and reduce the activity of P-GSK-3?in the brain of AD mice.Our results provide experimental evidence that Evo can serve as a neuroprotective candidate for the prevention and/or treatment of neurodegenerative diseases.