Study On The Acute Toxicity Test And Improvement Effect Of Learning And Memory Abilities By AD Model Mice In The Aerial Parts Of Polygala Tenuifolia Willd.

Alzheimer’s disease（AD）is a chronic neurodegenerative disorder characterized primarily by memory impairment and cognitive impairment.Learning and memory dysfunction is the main clinical manifestation of AD patients.And it is of great significance to find improvement learning and memory drugs from traditional Chinese herbal medicines with low toxicity and good curative effect.The aerial parts of Polygala tenuifolia Willd.,which are also known as the"Xiao Cao"and contained in the Shennong’s Herbal Classic of Material Medica,are the dry aerial parts of this plant.“Xia Cao”is included in the local Chinese medicine decoction processing regulations in some provinces in China,and recorded the effects of treating convulsions,forgetfulness,cough,phlegm,and hemorrhoids.Studies have confirmed that it contains chemical components such as flavonoids,saponins,polysaccharides,etc.,and has biological activities such as anti-oxidation and anti-inflammatory.The previous research of this group found that the aerial parts of the Polygala tenuifolia Willd.have a good effect of delaying the aging of the body.And aging is an important factor in the pathogenesis of AD and memory loss.Therefore,the aerial parts of the Polygala tenuifolia Willd.were used as the research object in this paper.This study evaluated its safety through acute toxicity experiments,and focused on its effect of improving the learning and memory by AD model mice,which provided experimental data for the development of it.The following are the main research contents and results of this paper.1.Acute toxicity studies were carried out on the aerial parts of Polygala tenuifolia Willd..The result showed that no LD₅₀ was detected,so the maximum administration dosage was tested.No death or poisoning was observed in the drug-administered group.There was no significant difference in body weight,blood biochemical index（ALT,AST,BUN and Crea）,and organ index between the drug-administered group and the normal control group（P>0.05）.And no obvious lesions were found in the organs in the drug-administered group.The maximum administration dosage of its extract was 20 g/kg（equivalent to 80 g/kg of the original drug）,which was 533.3 times the maximum clinical daily dose in adults.2.This experiment used scopolamine-induced learning and memory impairment model mice to study the improvement of learning and memory in the aerial parts of Polygala tenuifolia Willd..The administration of it could shorten the latrncy time of Morris water maze test and increase the crossing numbers.In the step down test,the latency could be prolonged and the number of errors could be reduced,indicating that it has the effect of improving learning and memory.Compared with the model group,it could increase the levels of ACh and ChAT and decrease the level of AChE in the hippocampus and cortex of mice,regulate the cholinergic nervous system;could increase the level of neurotrophic factor BDNF in the hippocampus and cortex;and could decrease the IL-1βlevel and elevated IL-10 level in the hippocampus and cortex,inhibit inflammation.It could also increase the levels of antioxidant enzymes SOD and GSH in brain tissue and inhibit lipid peroxide MDA production.3.The AD mouse model made by using D-galactose combined with sodium nitrite was used to study the effect of improving the learning and memory in the aerial parts of Polygala tenuifolia Willd..The results of Morris water maze test,step-down test and dark-avoidance test showed that it could significantly improve the learning and memory abilities of mice.The high-dose group and the root of Polygala tenuifolia Willd.group had similar therapeutic effects,and there was no significant difference in behavioral scores（P>0.05）.Compared with the model group,it could increase the levels of ACh and ChAT and decrease the level of AChE in the hippocampus and cortex of mice;could decrease the IL-1βlevel and elevated the IL-10 level in the hippocampus and cortex.It could also increase the levels of antioxidant enzymes SOD and GSH in brain tissue and inhibit lipid peroxide MDA production.Western blot,RT-qPCR and immunohistochemistry were used to study the effect of it on BDNF-TrkB signaling pathway.The results showed that it could increase the protein and mRNA expression of BDNF and TrkB in the hippocampus of mice,and up-regulate the protein expression of BDNF and TrkB in the hippocampal CA1 region.