Study On Anti Alzheimer's Disease Effect Of Fibraurea Recisa Pierre Alkaloid And Its Mechanism

Alzheimer's disease?AD?is a chronic neurodegenerative disease.The main clinical manifestations are decreased cognitive ability and memory loss,accounting for 60-80%of the total number of dementia.At present,there are few drugs for treating AD on the market,and synthetic drugs are one of the most important methods for treating the disease,mainly including acetylcholinesterase inhibitors and glutamate receptor antagonists.A large number of studies have shown that although synthetic drugs can improve the various functions of AD patients,such treatments only relieve symptoms and only work on one or several links in the pathogenesis,so it can not prevent the deterioration of the disease,and it is not good.The reaction is obvious.Compared with chemical synthetic drugs with high side effects on the market,natural drugs have multi-target and multi-link functions,which play an increasingly important role in the treatment.At present,scholars at home and abroad have extensively carried out research on medicinal plants against Alzheimer's disease,and found many active ingredients with anti-AD effects.The dried cane of Fibraurea recisa Pierre is mainly composed of isoquinoline alkaloids represented by Fibraurea recisa Pierre,which has anti-tumor,anti-osteoarthritis and anti-virus.And pharmacological effects such as neuroprotection,its preparation is mainly used for various infections in the clinic,safe and effective.For the first time,our research team found that the alkaloids of the Fibraurea recisa Pierre have a significant improvement effect on the animal model of Alzheimer's disease.The purpose of this thesis is to further study and explore the anti-AD effect and mechanism of alkaloids of Fibraurea recisa Pierre,and provide a scientific basis for the further development and utilization of alkaloids.This study used D-galactose/AlCl₃ to induce mouse Alzheimer's disease model,and observed the alkaloids of Fibraurea recisa Pierre by behavioral detection,HE pathology,ELISA,immunohistochemistry and Western blotting.Anti-AD action and mechanism of action.The results of behavioral tests indicated that alkaloids from the Fibraurea recisa Pierre could significantly improve the spatial short-term working memory ability of the AD model mice in the Y-maze test and the spatial learning and memory ability in the Morris water maze.The results of ELISA showed that alkaloids from the Fibraurea recisa Pierre could significantly reduce the levels of amyloid?A??,P-Tau,Tau,CDK5 and acetylcholinesterase?AchE?in the brain of AD model mice,which could significantly increase the model mice.The levels of the neurotransmitters acetylcholine?Ach?,choline acetyltransferase?ChAT?and MAP2 in brain tissue.In the study on the anti-oxidation effect of alkaloids from the Fibraurea recisa Pierre,it was found that the alkaloids of the Fibraurea recisa Pierre could significantly increase the glutathione?GSH?and catalase?CAT?in the AD model mice induced by D-galactose/AlCl3.And the activity of superoxide dismutase?SOD?reduces the levels of oxidative stress products malondialdehyde?MDA?and nitric oxide?NO?.In the anti-inflammatory effect of alkaloids of the Fibraurea recisa Pierre,it was found that the alkaloids of the Fibraurea recisa Pierre can significantly reduce the levels of tumor necrosis factor-??TNF-??and interleukin-1??IL-1??in the brain tissue of AD mice.Significantly reduced the expression levels of nuclear transcription factor-?B?NF-?B?,cyclooxygenase-2?cox-2?and induced nitric oxide synthase?iNOS?in brain tissue of model mice.In addition,immunohistochemistry also detected that alkaloids from the Fibraurea recisa Pierre significantly reduced the levels of inflammatory factors interleukin-33?IL-33?and ST2 protein in the brain tissue of model mice.In the study on the anti-neuronal apoptosis effect of alkaloids from the Fibraurea recisa Pierre,the alkaloids of the Fibraurea recisa Pierre significantly inhibited the protein expression of Caspase-3,cleaved Caspase-3 and Bax in the brain of AD model mice,and increased Bcl-2protein expression,with anti-neuronal cell apoptosis.H&E and TUNEL staining showed that alkaloids from the Fibraurea recisa Pierre significantly inhibited neuronal apoptosis.The above results indicate that the alkaloids of the Fibraurea recisa Pierre have a significant improvement effect on D-galactose combined with aluminum trichloride-induced Alzheimer's disease in mice,and its anti-AD effect is through anti-oxidative stress,anti-neuroinflammation and anti-nerve.Apoptosis is achieved.