Effects And Possible Mechanism Of β-asarone On Cognitive Impairment In AD Model Rats

Alzheimer’s disease(AD)is a degenerative disease of the nervous system,which is more common in the elderly.Aβ deposition may be the main cause of AD.Shichangpu is China’s traditional Chinese medicine with nourishing brain and brain.Its main active ingredient is β-asarone(β-asarone).There are literatures indicating that Shichangpu is used clinically to treat epilepsy and other neurological diseases Good curative effect,so this article aims to investigate whether β-asarone can rescue the cognitive impairment of AD model rats caused by stereotaxic injection of Aβ oligomers,and explore the relevant molecular levels in the brain after administration of β-asarone.Mainly include the following results:1.β-Asarone can inhibit the polymerization of Aβ1-42 monomers to form oligomers and can decompose the Aβ oligomers produced,and can enter the brain through the bloodbrain barrier.The experimental system is DMEM medium and the final concentration of Aβ1-42 monomer is 2 μmol / L,the concentration of β-asarone treatment is 0.156,0.625,2.5,10,40 μg / m L,the experiment is divided into two groups,respectively-Asarum coincubation group with Aβ and the pre-incubation group where β-asarone was added after Aβ was incubated alone to form oligomers,Th T method was used to detect the formation of Aβ oligomers under different concentrations and treatments.It was found that under the treatment of the co-incubation group,β-asarone could inhibit the formation of oligomers of Aβ monomer,and the inhibitory effect was concentration-dependent;while the test results of the pre-incubation group showed the same change trend,that is,β-asarone Ether has a decomposition effect on pre-formed oligomers.Secondly,we used TEM imaging,the image results further verified the accuracy of the results,and HPLC detection proved that β-asarone can pass through the blood-brain barrier,enter the brain and be absorbed by cells.2.β-Asarone treatment can improve learning and memory impairment in AD-modeled rats,and inhibit the loss of CA1 and DG dendritic spines in hippocampus.The experimental animals were Sprague Dawley(SD)rats,which were divided into six groups with a total of 72 rats and five groups of rats were injected with Aβ oligomers dissolved in 1 × PBS on the hippocampus on both sides,and the remaining group was injected with the same amount of 1 × PBS for cultivation Two weeks after recovery,the rats injected with Aβ were randomly divided into AD model group,memantine administration group and β-asarone 2.5 mg/kg,10 mg/kg,40 mg/kg low,middle and high dose groups.The way of medicine is intraperitoneal injection,and the continuous administration time was 14 d.After the drug delivery was completed,the water maze test,Nissl staining and Golgi staining test were used to explore the effects of drug delivery on learning and memory,the number of neurons in the cortex and hippocampus,and dendritic spine density in AD rats.Behavioral experiment results show that the administration of β-asarone can improve the learning and memory impairment of AD model rats,and it has a dose-dependent;The results of Nissl staining and Golgi staining showed that β-asarone can restore the loss of neurons in the cortex and hippocampus and the decrease in the number of dendritic spines caused by Aβ.3.The effect of β-asarone treatment on the level of oxidative stress and the expression levels of glycogen synthase kinase-3(GSK-3β)and β-catenin in AD model rats.Fluorescent quantitative polymerase chain reaction was used to detect the m RNA levels of antioxidant enzymes SOD and GSH-Px in AD model rats after administration of β-asarone,and the accuracy of q PCR results was further determined by kit testing;protein immunity The expression of GSK-3β,p-GSK-3β,and β-catenin in the hippocampus of AD-modeled rats was tested by blotting.The results show that β-asarone can reduce the oxidative stress damage caused by Aβ,restore the phosphorylation level of GSK-3β,and then inhibit the intracellular degradation of β-catenin.In summary,β-asarone can pass through the blood-brain barrier and has the effect of inhibiting the aggregation of Aβ monomers and decomposing their oligomers;while in vivo studies have shown that β-asarone can reduce the effects of Aβ Oxidative stress restores the normal level of intracellular β-catenin,thereby inhibiting the loss of neurons and the decrease in dendritic spine density,saving the cognitive impairment of AD model rats.The research results have certain application value for the development of potential AD control drugs and food.