The Ameliorating Effects Of Water-soluble Ginseng Oligosaccharides On Scopolamine Induced Learning Disorder

Learning and memory is an important function of the brain and anecessary feature for human life. The hippocampus is closely related tolearning, memory and cognitive function. Structural or functional changesin the hippocampus would lead to cognitive impairment. Alzheimer’sdisease (AD) is a progressive neurodegenerative brain disorder, and itsneuropathological feature is the loss of nerve cell in the hippocampus andbasal forebrain, resulting in degeneration of the memory capacity.Multiple theories such as the cholinergic theory and the oxygen freeradical theory have been involved in the pathogenesis of AD. Thecholinergic theory, which is characterized by deficiencies of acetylcholine (ACh), has been considered the impairment of cholinergic neurons andneuronal dysfunction in the brain of Alzheimer’s disease patients. Theoxidation free radical theory, which is characterized by increase ofoxyradical, has been considered induction of lipid peroxidation andcausing neuronal degeneration, denaturation and apoptosis in Alzheimer’sbrain.ACh is an important neurotransmitter involved in learning andmemory. The cholinergic nerve endings can release ACh and ACh exertsphysiological effect through two receptors, nicotinic receptors andmuscarinic receptors, in central nervous system. The termination of ACheffect depends on acetylcholinesterase (AChE), which can decomposeACh, in the cholinergic synaptic cleft. Some Researches have showedthat memory function principally depends on ACh content in brain and isattenuated when ACh is lower level. In the brain of AD patients, ACh content was significantly reduced, causing memory and cognitivedysfunction. Therefore, AChE inhibitors have been used to treat cognitiveimpairment in AD patients.Oxidative stress is also one of the main affecting factors in AD, soseveral antioxidants have been studied for the reduction of oxidativestress occurring in the brain of the patients. Catalase (CAT), which is anenzyme catalyzed decomposition of hydrogen peroxide, is an importantfree radical scavenger in vivo and plays an important role in preventinglipid peroxidation. Therefore, CAT could maintain learning and memoryabilities due to preventing neuronal degeneration and apoptosis anddelaying neurons senescence. Several antioxidants such as vitamin E,melatonin and monoamine oxidase B inhibitors have been tested for theadjuvant treatment of AD in therapeutics. They could activate, protect andrepair the neurons, and could improve the function of brain cells, so they play a role in anti-aging and amelioration learning and memory.Ginseng is root of Araliaceae perennial herb and its infusions orextracts are reported to be effective for a large number of medicalproblems associated with aging, including essential hypertension andmemory loss. Ginseng contains multifold chemical active componentswhich including saponins, polysaccharides, oligosaccharides,polypeptides, fatty acids, amino acids and aetherolea. During the pastdecades, numerous researchers have focused on structures andbioactivities of ginsenosides and ginseng polysaccharides. As for thevaluable oligosaccharide in ginseng, the reports are quite limited.The digestion and absorption of ginseng oligosaccharides iseffortless in intestinal tract and its utilization rate is higher in vivo,because it has simple molecular structure and small molecular weight.Some researches found that ginseng oligosaccharides can significantly enhance the function of immune system. Recently, it has been reportedthat oligosaccharides have a significant effect in treatment of cognitiveimpairment caused by deficiency of ACh. Based on these studies, weinjected intraperitoneally water-soluble ginseng oligosaccharides(designated as WGOS), which were obtained form warm-water extract ofPanax ginseng roots, in memory impairment mice induced byscopolamine (Scop) to detect therapeutic effect of WGOS throughbehavioral and biochemical experiments. Our research showed:1. During the training days of Morris water maze, the mean escapelatency was gradually shortened in both the saline alone and WGOS40,WGOS80alone mice and no significant difference among the treatmentgroups (P＞0.05), indicating that the WGOS could not influence spatiallearning capacity in normal mice. The mean escape latency was almostconstant in Scop alone group during training days, demonstrating that spatial learning capacity was decreased after Scop administration.However, WGOS40+Scop and WGOS80+Scop group showed that themean escape latency approach to saline control group (P﹥0.05) and itwere significantly shorter than the Scop alone group (P﹤0.01),suggesting that WGOS could improve Scop-induced spatial learningdeficits.2. During the test of place navigation in Morris water maze, themean escape latency and total distance were no significant differenceamong saline alone and WGOS40, WGOS80alone mice (P﹥0.05),indicating that WGOS could not influence memory capacity in normalmice. The mean escape latency and total distance were significantlyhigher in Scop alone group than the saline group(P﹤0.01), demonstratingdecreased memory capacity after Scop administration. However,WGOS40+Scop and WGOS80+Scop group showed that the mean escape latency and total distance approach to the saline control group (P﹥0.05) and were significantly lower than the Scop alone group (P﹤0.01),suggesting that WGOS could improve Scop-induced memory deficits.3. During the test of spatial search in Morris water maze, we testedfour indexes, the frequency traversed the platform and active area, totaldistance in each treatment group. They were no significant differenceamong saline alone and WGOS40, WGOS80alone mice (P>0.05),indicating that WGOS could not influence spatial memory capacity innormal mice. They was significantly higher in Scop alone group than thesaline control (P <0.01), demonstrating decreased spatial memorycapacity after Scop administration. However, WGOS40+Scop andWGOS80+Scop group showed that those indexes approach to the salinecontrol group (P﹥0.05) and were significantly lower (P﹤0.01) than theScop alone group, suggesting WGOS could improve Scop-induced spatial memory deficits.4. After behavioral tests, we measured the ACh content in micehippocampus of each treatment group. Our result indicated that AChcontent in hippocampus was no significant difference among saline aloneand WGOS40, WGOS80alone mice (P>0.05), indicating that WGOScould not influence the ACh content in hippocampus of normal mice. TheACh content was significantly lower in hippocampus of Scop alone micethan the saline control group (P <0.05). However, WGOS40+Scop andWGOS80+Scop group showed that the ACh content in hippocampusapproach to the saline control group (P>0.05), and was significantlyhigher than the Scop alone group (P <0.05), suggesting WGOS couldimprove Scop-induced the ACh content in hippocampus.5. We also measured the AChE activity in hippocampus of eachtreament group. Our result indicated that the AChE activity in hippocampus was no significant difference among saline alone andWGOS40, WGOS80alone mice (P>0.05), indicating that WGOS couldnot influence the AChE activity in hippocampus of normal mice. TheAChE activity in hippocampus was significantly higher in Scop alonegroup than the saline control group (P <0.05). However, WGOS40+Scopand WGOS80+Scop group showed that the AChE activity inhippocampus approach to the saline control group (P>0.05) and wassignificantly lower than the Scop alone group (P <0.05), suggesting thatWGOS could improve Scop-induced increasing of the AChE activity inhippocampus.6. We also measured the CAT activity in hippocampus of each treamentgroup. Our result indicated that the CAT activity in hippocampus was nosignificant difference among saline alone and WGOS40, WGOS80alonemice (P>0.05), indicating that WGOS could not influence the CAT activity in hippocampus of normal mice. The CAT activity inhippocampus was significantly lower in Scop alone group than the salinecontrol group (P <0.01). However, WGOS40+Scop and WGOS80+Scop group showed that the CAT activity in hippocampus approach to thesaline control group (P>0.05), and was significantly higher than the Scopalone group (P <0.01), suggesting that WGOS could improveScop-induced reduction of the CAT activity in hippocampus.In conclusions, the present study demonstrates that WGOS couldsignificantly improvement Scop-induced spatial learning and memorydefects, but could not influence learning and memory in normal mice.WGOS had therapeutic efficacy for Scop-induced learning and memorydefects by concurrently acting on multiple mechanisms, includingdecreasing ACh content, inhibiting AChE activity and augmenting CATactivity in hippocampus. Therefore, WGOS may be a potential drug for the treatment of AD.