Study On The Effect Of Fibrauretine On AD Model Induced By Aβ_1-42 In Mice And And The Way Of Trans Barrier Transport

Alzheimer’s disease(AD)is a kind of chronic neurodegenerative disease.The main clinical manifestations are cognitive decline and memory loss,which mostly occur in the elderly [1].It seriously damages the physical and mental health of the elderly and brings heavy burden to the family and society.The high incidence rate and high mortality rate of AD have become the main problems affecting human health.It has attracted wide attention from scientists and has become a hot and difficult topic in the field of medicine research.At present,the drugs on the market for the treatment of AD are chemical synthesis,which can not prevent the progress of AD,and the adverse reactions are obvious,and the side effects are large.Due to the advantages of multi-target,multi link and relative safety of natural drugs,it is an important strategy to find effective components from natural products for the development of new drugs for AD.Studies on absorption and oral bioavailability of palmatine and jatrorrhizine in Huangteng in ratsFibrauretin is an isoquinoline alkaloid isolated from the stem of Fibraurea recisa Pierre.It is safe and effective for anti infection in clinic.We found for the first time that berberine can significantly improve Alzheimer’s disease in mice induced by D-galactose combined with aluminum trichloride,and therefore obtained the national patent for invention.In order to further study the anti ad mechanism of rotenone,we made AD model by injecting amyloid beta protein into mice brain ventricle The expression levels of IRS-1,PI3 K,Akt,GSK-3 β,NF-κ bp65,Bcl-2 and Bax proteins were detected by blot.The aim of this study was to explore whether roteinin could exert its neuroprotective effect by regulating PI3 K / Akt / GSK-3 β signaling pathway in anti apoptotic,anti-inflammatory and antioxidant processes.The results of this study show that rotenone can significantly improve the symptoms of ad induced by aβ1-42,and its antioxidant,anti-inflammatory and anti apoptotic effects depend on PI3 K / Akt / GSK-3βsignal transduction pathway.The results indicate that the drug can be absorbed into the blood through the intestinal barrier,and then through the blood-brain barrier to play a role.What kind of transport mode does the drug transport across the membrane? What is the transport mechanism? So far,there is no research.In order to further study the transmembrane transport mode and mechanism of fibrin,Caco-2cell monolayer model and MDCK-MDR1 cell monolayer model were used to simulate the intestinal barrier and blood-brain barrier respectively.The safe concentration range of fibrin was determined by MTT colorimetry.After modeling,the monolayer cell resistance was measured,and the P-gp activity expressed by cells was detected to judge whether the membrane was successfully constructed The effects of different time,concentration,temperature and P-gp inhibitor on the two-way transport of rotenone were investigated.The results of this study showed that the active transport from BL side to AP side was dominant,and the passive transport from AP side to BL side was dominant.The efflux of P-gp was significantly reduced,and the substrate of P-gp was luteolin.In the blood-brain barrier model,the passive transport is dominant and the active transport also contributes to it.Verapamil,an inhibitor of P-gp,can significantly inhibit the absorption of fibrin.Fibrin may be a substrate of P-gp.This study will provide basic research data for the research of luteolin as a new anti AD drug in the future.