Neuroprotective Effects Of Water-soluble Ginseng Oligosaccharides On Scopolamine-induced Cognitive Impairment And Inflammatory Respomse

Alzheimer disease (AD) has become a major public health problem followinglife extension in human. AD is a neurodegenerative disease, and its characterization inpathology is senile plaques and neurofbrillary tangles induced by of the excessiveamounts of amyloid β protein and tau protein. The notable symptom of AD isdeterioration of the cognitive functions and changes of social adaptability. Theincidence of AD is affected by many factors and pathological mechanism is verycomplex. So, it is most important for us to find the effective treatment therapy andmeans of AD.Our previous study has found that water-soluble ginseng oligosaccharides(WGOS) could shorten the mean escape latencies and increase the number of crossingthe hidden platform, indicating WGOS could improve learning and memory in ADmouse. Meanwhile study confirmed that WGOS could increase acetylcholine (ACh)levels through inhibiting the acetylcholinesterase activity in hippocampus of ADmouse, suggesting that WGOS could improve learning and memory. Based on theresults, we observed neuroprotective effect of WGOS on the scop-induced animalmodel of AD and its mechanism from three aspects: behavioral, morphological andimmunological. It can provide a basis to develop a safe and effective prevention andnew drug treatment of AD.Objective: To evaluate the effect of WGOS on scopolamine-induced amnesia inmouse using novel object recognition task and to explore the protective mechanismeffect of WGOS on the hippocampal neurons.Methods: Experimental mouse were randomly divided into six groups as follows: normal (saline group), drug (WGOS40group, WGOS80group), model (Scop group)and treatment (WGOS40+Scop group, WGOS80+Scop group). Firstly, Memoryimpairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist.Anti-amnesic effects of WGOS were measured by novel object recognition task inmice. Secondly, we examined the levels of tumor necrosis factor-a (TNF-a) andinterleukin-1β (IL-1β) using enzyme-linked immunosorbent assay (Elisa). Finally, thechanges of morphology and number of astrocyte was observed byimmunohistochemical staining in the hippocampus of mice.Results: Our present results show that:①WGOS reverse cognitive impairmentinduced by scopolamine in novel object recognition task. During the training andretention sessions, one-way ANOVA analysis indicated that the total time in exploringthe objects was not signifcantly different among the groups, while the time spent inexploring the novel object was signifcantly different during the retention session. Thescopolamine decreased signifcantly the discrimination index compared with vehicle,suggesting an amnesia role for scopolamine. Pre-treatment with WGOS (40,80mg/kg)increased signifcantly the discrimination index in WGOS40+Scop and WGOS80+Scop groups, when compared with Scop group.②The Elisa analysis demonstratedthat Scop administration increased significantly the hippocampus and the serum IL-1βproteins expression in the mouses. The expression of IL-1β protein in thehippocampus and the serum due to Scop-induced memory impairment wassignificantly restored in WGOS40+Scop and WGOS80+Scop groups, as comparedto Scop group. The expression of TNF-α protein in the serum was also markedlyincreased in the Scop group, as compared to the Saline group. The expression ofTNF-α protein in the serum due to Scop-induced memory impairment wassignificantly restored in the WGOS (40,80mg/kg) group, as compared to Scop group.③Non-activated astrocyte and activated astrocyte were observed in hippocampus inthe vehicle-treated controls and Scop group through the GFAP staining. The numbersof GFAP-positive cells were increased markedly in the CA1, CA3and dentate gyrus(DG) of the hippocampus by Scop administration. WGOS at the dose of40mg/kg could inhibit the number of GFAP-positive cells, compared with Scop group.Conclusion: Our results indicate that scop-induced cognitive impairment isameliorated by WGOS in part through the suppression of scop-induced fammationincluding astrocyte activation and TNF-α and IL-1β expression. These novel findingsfurther demonstrate that WGOS may potentially be developed as AD therapeuticdrugs for different severities of neurodegenerations.