Effect Of Ligustilide On A? Transport And Clearance Via Regulating GLUT1 In The Brain Microvascular Endothelial Cells Of Animal Models With Alzheimer's Disease

ObjectiveAlzheimer's disease is one of the most common types of dementia.Clinically,it is characterized by the deposition of amyloid plaques around the neurons in the brain and tangles of nerve fibers in the neurons.The real cause of alzheimer's remains unclear.For the treatment of AD,there is no effective treatment for drugs,so it is urgent to find effective treatment drugs.Epidemiological studies have found that,in western developed countries,the incidence of AD decreases due to increased attention to blood vessels and brain health.Targeting to Blood–brain barrier and removing deposits of amyloid plaques might be able to provide new method for treatment of AD.The purpose of this study was to explore the pharmacological effects of Ligustilide on improving the learning and memory ability of the model animals of alzheimer's disease.MethodsIn this study,we used the classic APP/PS1 double transgenic mouse model to explore the protective role of Ligustilide.16 wild type mice with the same month age were selected.Grouping: normal control group,the APP/PS double transgenic mice were divided into 3 groups at random,model group,Ligustilide low dose(10 mg/kg),Ligustilide high dose(20 mg/kg).From the age of 10 months,mice were given a daily dose of Ligustilide.The control group and the model group all gave DMSO solvent.The behavioral test was started after 8 weeks.Mechanism study: Western blotting and other methods were used to determine the correlation protein of the A ? metabolic pathway and its downstream cascade.ResultsThe Morris water maze and the Y maze test results showed that the gastric feeding of Ligustilide(10 mg/kg/day and 20 mg/kg/day)to the APP/PS1 double transgenic mice improved learning and memory ability.Ligustilide mainly affects GLUT1/LRP1/RAGE in cerebral microvascular endothelial cells,which improves A? transportation and clearance,and reduces the deposition of A? in the brain.Ligustilide improved the metabolism of A?-related pathways(ADAM10,BACE1,NEP,IDE,sAPP ?,RAGE and LRP1),reduced the neural degenerative diseases(NGF,SYN,PSD93,PSD95,BDNF),oxidative stress(ROS,MDA),apoptosis(BAX,BCL-2,CASPASE-3),neuroinflammation(IL-6,IL – 1?,NF? B,NLRP3)and endoplasmic reticulum stress levels.ConclusionThese results indicate that Ligustilide directly targets to GLUT1,which located in the cerebral microvascular endothelial cells,to promote A ? transportation and clearance.Thus,Ligustilide improves the learning and memory ability of AD animal model and provides a new treatment strategy in patients with AD.