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Ginsenosides Rg1 could improve learning and meomry abilities in dementia
Alzheimer’s disease (AD) is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death. In 2006, there were 26.6 million people worldwide with AD. Alzheimer’s is predicted to affect 1 in 85 people globally by 2050. Alzheimer’s disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions, leading to degeneration and gross atrophy of the affected regions such as the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD. There is no cure for Alzheimer’s disease; available treatments offer relatively small symptomatic benefit but remain palliative in nature. Dr. Zhang, from Shandong University, China, found that Rg1, a ginsenoside extracted from Ginseng, is able to improve the learning and memory abilities in rat dementia induced by D-galactose introperitoneal injection. In the experiment, rat dementia model was successfully created by D-galactose intraperitoneal injection plus ovary surgical removal. Rg1 injection at 5-20mg/kg/d significantly restored impaired cognitive capacity in demented rats, the time of crossing Morris water maze was shorted, and the number of crossing maze was increased, in a dose-dependant manner. Also, Rg1at 10mg/kg/d reduced the beta-amyloid accumulation by 1/3. ADAM10 is an important protease cleaving beta-amyloid precursor protein, and its reduction is commonly seen in Alzheimer’s disease. However, BACE1 is positively related to dementia. In this experiment. Rg1 injection markedly restored the level of ADAM10, the neuron cells positive of ADAM10 staining increased from 12% in demented rats to 66% after Rg1 intervention. In contrast, the level of BACE1 reduced from 62% to 19% after Rg1 injection. Furthermore, caspase 3, an enzyme involved apoptosis initiation, was activated in brain hippocampus in dementia model, but was reduced after Rg1 treatment. Above results suggest ginsenoside Rg1 increases cognitive capacity in demented rats through increasing ADAM10 level, reducing BACE1 and caspase 3 activities. The finding implies that ginsenoside Rg1 could be of potential therapeutical value in treatment of Alzheimer’s disease. The following the abstract of this doctoral dissertation: 該研究中首先探討了利用去卵巢結合D-半乳糖腹腔注射建立大鼠AD模型的可行性,發現去卵巢結合D-半乳糖腹腔注射處理的大鼠行為學改變以及海馬病理學改變均符合AD疾病情況下的變化,提示造模成功。然後,我們研究了人參皂苷Rg1對AD大鼠模型學習和記憶的影響。同時還研究了活化的含半胱氨酸的天冬氨酸蛋白水解酶caspase3的變化情況,以明確人參皂苷Rg1對AD模型大鼠神經元凋亡的影響。 1.研究對象及分組:將96只Wistar大鼠隨機分為兩組,一組72只行去卵巢手術,另一組24只行假手術,術後行抗炎處理。將假手術組大鼠隨機等分為兩組:一組按1ml/kg/d在大鼠腹部皮下注射生理鹽水(CT),另一組按100mg/kg/d腹腔注射D-半乳糖(D );去卵巢手術組大鼠隨機等分為六組。 2.研究內容:
結果 1.去卵巢結合D-半乳糖腹腔注射能夠顯著損害大鼠的認知功能,引起大鼠海馬內Aβ1-42的高表達。
2. 人參皂苷Rg1和雌激素能夠顯著改善模型大鼠的學習和記憶能力
3. 人參皂苷Rg1和雌激素促進模型大鼠學習和記憶能力的機制研究
結論
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