| Alzheimer's disease (AD) is a kind of degenerative disease with a high incidence in the elderly. The main symptoms of the patients are progressive memory loss and cognitive dysfunction, which seriously do harm to human health and life. The incidence of AD showed a rising trend in recent years. As the incidence of AD is affected by many factors, its etiopathogenisis and pathological mechanisms are very complex, so that there is still lack of effective treatments at present.One of the typical pathological changes in AD brain is that a large number ofβ-amyloid protein (Aβ) abnormally accumulating in lesion area. It is now generally agreed that Aβis the common pathway of a variety of agents inducing AD and the key factor leading to AD onset. Searching for effective prevention and treatment is the hot spot of AD research nowadays.Development of Traditional Chinese Medicine has been a long history with thousands of years. The number of drugs which could effectively improve cognition and prevent memory loss is increasing. Ginseng is a rare herb of Traditional Medicinal, and the active component, Ginsenoside Rb, Rg, have been demonstrated to improve cognitive and memory function. However, whether another monomer, Ginsenoside Rd, possess this effect is still an open question.This topic took the question as a starting point, investigated the effect of Rd on the experimental AD and the internal mechanisms in vivo and in vitro, and provided basis for searching effective prevention and treatment means of AD. Objective To identify neuroprotective effects of Rd on experimental AD and to explore possible mechanisms, supplying experimental evidence for using Rd as a kind of clinical prevention and treatment means for AD in the future.Methods (1) Aβ40 was injected into adult rat hippocampal CA1 area with stereotaxic apparatus to produce model of acute brain injury, and different doses of Rd were given through intraperitoneal injection. Then the neuroprotective effects of Rd and the effective concentrations were determined by investigating behavior, ultrastructure of injury region, neurons, glias, and cytokines detection. (2) APP transgenic mice received long-term intervention of Rd, and the indes to evaluate the role of Rd is same to the former, so that the neuroprotective mechanisms of Rd were discussed from the perspective of inflammatory responses. (3) Primary culture of rat hippocampal neurons was affected by using Aβ35-35 to induce neuronal damage, and was intervened by receiving different doses of Rd. Then the neuroprotective effects of Rd and the effective concentrations were determined by analyzing morphological and molecular biological results. In addition, by taking probucol and edaravone as positive control drugs, the mechanisms of Rd were further investigated from the perspective of oxidative stress.Results (1) The Rd concentrations of 10 and 30mg/kg both possessed neuroprotective effects on Aβ40 induced acute brain injury of rat, reduced the escape latency in the water maze, increased in the number of crossing the platform, reduced the loss of neurons in CA1 area and inhibited apoptosis, repressed excessive activation of glial cells and cytokine secretion, and protected mitochondria and synaptic ultrastructures. (2) Rd 10mg/kg could improve learning and memory of APP transgenic mice, and inhibited brain inflammation. (3) Rd 10μM depressed toxicity of primary cultured hippocampal neurons induced by Aβ25-35, inhibited cell apoptosis, and lessoned oxidative stress injury.Conclusion Ginsenoside Rd could inhibit inflammation in hippocampus, reduce damage of hippocampal neurons, and ultimately improve learning and memory of experimental AD animals. In addition, Rd could also inhibit neuronal oxidative stress response and protect neurons against the toxic effects of Aβ.
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