Screening Of Acholinesterase Inhibitors And Study Its Inhibition On Mice Of Alzheimer's Disease

Alzheimer (dementia, Alzheimer's disease, AD) is mental illness characterized by impairment of memory. In June 2007, an international conference on prevention of AD held by AD Association reported that there would be 26 millions patients suffering from AD in 2006 and the number woule increased to 106 millions by 2050. It has become a difficult disease which influences the quality of old people's life following the diseases of heart, brain vessel and malignant tumor. At present, the cause of this disease has not been fully elaborated yet, and the treatment of AD is also a thorny problem. The change of central cholinergic transmision mechanism is the most remarkable lesion of the patients, associated with the severity of AD. In recent years, cholinesterase inhibitors are cosiderded as the first choice in treatment. In order to provide more choices to prevention and cure AD and its complications in clinic, developing more and more effective acetylcholinesterase inhitors from plants has become one of the focuses at home and abroad.Objective Purpose of this study is to screen out acetylcholinesterase inhibitors from some plant extracts to provide the lead compounds for development of new drugs to Alzheimer's disease.Methods The brain tissue of rats was taken as an experimental subject and a sulfuric acid neostigmine was taken as a positive control. An AchEIs screening model was established in vitro. The extracts of plants were randomly screened with the model. The inhibitors were traced from active extracts.Based on the research work above, a aluminum chloride-induced Alzheimer's mice model was established. The effect of Cannabichromeorcinic Acid on the level of learning and memory, and the inhibition on AchE of brain tissue and serum were studied with the model.Results The positive control, neostigmine sulfate had significantl inhitory activity and the results of dozens of total plant extracts'were positive.24 samples with activity were screened out from more than 30 types of isolated segments. The inhibitors of these samples were traced.27 new samples with activity were screened out from more than 30 kinds of small segments from these samples. In the end, some inhibitors were obtained. They are Scopoletin, Cannabichromeorcinic Acid, Quercetin, Nicotinic Acid, Gallic, Nethylester, Protocatechuic Aldehyde, Magnolol, Honokiol, Sobean and Rutin.The results in vivo accord with the anticipation showed by the results in vitrol. The results showed that Cannabichromeorcinic Acid could significantly increased the level of learning and memory of Alzheimer's mice; and it could inhibit the acetylcholinesterase in brain tissue and serum of Alzheimer's mice. The low dose group did better. However, the positive (piracetam) group had the best strength.Conclusions The model in vitrol is convenient and reliable. It can be used to screen out the inhibitors. These extracts with activity can be examined in depth. Cannabichromeorcinic Acid can be researched further as lead compounds to develop new drugs for AD.