Anti-inflammatory Effect Of Esculentoside A In Aβ-Induced Inflammation Of Primary Microglial Cells:A Basic Study And Explanation Of Its Mechanism

Background:Alzheimer’s disease(AD)is a chronic neurodegenrative disease of central nervous system.However,the underlying molecular mechanism of AD remains elusive.Amyloid-β(Aβ),the main component of neuritic plaques,is considered as the leading factor of AD.Recently,accumulated evidences show that neuroinflammation plays an important role in the pathogenesis of AD.Aβ induced microglia-mediated neuroinflammation is the key event leads to synaptic injury and neuronal dysfunction.At present,there is no effective treatment for AD in clinical.Chinese medicine has rich theoretical research foundation and has been experienced in clinical practice for dementia.Therefore,the application of traditional Chinese medicine to treat AD shows broad prospects.Esculentoside A(EsA)is the main chemical constituent in Shang Lu,a Chinese traditional medicine,which has much pharmacological effects such as anti-inflammatory,antibacterial,antiviral,and diuretic properties.It has been shown that EsA has the potential to treat neuroinflammatory disease.Objectives:To study the effect and the underlying mechanisms of EsA on Aβ1-42-induced neuroinflammation in mice priamry microglial cells.Methods:The mice primary microglia were treated with Aβ1-42 to simulate neuroinflammation in vitro.The effect of EsA on the viability and configuration of mouse primary microglial cells was detected by CCK8 assay and immunofluorescence.ELISA,RT-PCR and Western blot were used to detect the expression of inflammation-associated molecules after being incubated with EsA in Aβ1-42 treated mice primary microglia.Besides,in order to explore the mechanism underlying anti-inflammatory property of EsA,changes of the expression and phosphorylation levels of MAPK and TLR4 signaling pathway related proteins were studied.Results:EsA reduced the production of NO and prostaglandin E2(PGE2)in mouse primary microglia after Aβ1-42 treatment,and decreased the mRNA and protein expression of inducible nitric oxide sunthase(iNOS)and cyclooxygenase-2(COX-2).EsA could depress the expression of inflammatory cytokines and chemokines,such as interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemotactic protein-1(MCP-1),and inhibit the activation of MAPK and TLR4 signaling pathways in Aβ-stimulated primay microglia.Conclusion:EsA could decrease the expression of inflammation related factors in mice primary microglia and the underlying mechanism might be associated with inhibition of activation of MAPK and TLR4 signaling pathways.