The Protective Effect Of Liquirtigenin On Alzheimer’s Disease By Inhibiting Inflammatory Response And Its Mechanism

Objective: Alzheimer’s disease(AD)is the most common neurodegenerative disease among the elderly.Inflammation is one of the main pathogenesis,while liquiritigenin(LG)is a kind of flavonoid monomer extracted from traditional Chinese medicine licorice,which has anti-inflammatory,anti-tumor and anti-oxidation effects.This paper mainly studies whether LG exerts protective effect on AD through anti-inflammatory effect.Methods: In the animal experiment,3-month-old female APP/PS1double-transgenic model mice were randomly divided into two groups,AD placebo group and liquiritigenin treatment group,and C57 mice were used as the normal control.The dose of the liquiritigenin treatment group was 30mg/kg,the normal control group and the AD placebo group were 1%cmc-na,and the three groups were all given gavage.After 90 days of drug treatment,Morris water maze was used to test the spatial learning and memory ability of mice.The number and size of senile plaques in brain were measured by immunohistochemistry.Western blot was used to detectthe expressions of inflammatory proteins NLRP3 and caspase-1 in the brain,the expressions of apoptosis-related proteins caspase-3,BAX and bcl-2,as well as the expressions of APP,BACE1,PS1 and CTF,and the expressions of inflammatory factors were detected by RT-PCR.In cell experiments,after LG treated N2A-APP cells,Western blot was used to detect the expressions of inflammatory proteins NLRP3 and caspase-1,and the expressions of apoptosis-related proteins caspase-3,BAX and bcl-2.In AD cell models,SiRNA and overexpressed ERβ were transfected in N2A-APP cells.Expression levels of ERβ,inflammatory proteins NLRP3 and caspase-1,and apoptosis-related proteins BAX and bcl-2 were detected by Western blot.Results: In vivo experiments showed that LG could improve the learning and memory ability of AD mice and reduce the generation of senile plaques in the brain by reducing the expression of BACE1,PS1 and CTF.LG can also reduce inflammation and apoptosis in the brain of AD mice,mainly by reducing the expression of inflammatory proteins NLRP3,caspase-1,and apoptosis-related proteins caspase-3 and BAX,and increasing the expression of bcl-2.In vitro experiments showed that LG could activate ERβ without significant effect on ERα.LG can reduce inflammation and apoptosis of N2A-APP cells,mainly by reducing the expression of inflammatory proteins NLRP3,caspase-1,mRNA expression of inflammatory cytokines Il-1β and TNF-α.The apoptosis-related proteinscaspase-3,BAX and Increase the expression of bcl-2.LG can reduce the expression of BACE1,PS1 and CTF.It was also found that the expression of ERβ had the same function as that of LG.Conclusion: the results suggest that LG can alleviate the inflammatory response and apoptosis both in vivo and in vitro and its mechanism may be related to the up-regulation of ERβ expression.