Effect of pachymic acid on neuroinflammation in rats with Alzheimer's disease by regulating the HMGB1/TLR4 signaling pathway
XIAO Gen
LIU Jing
Abstract：Objective To investigate the effects of pachymic acid(PA)on neuroinflammation in rats with Alzheimer's disease(AD)by mediating the high mobility group box 1/Toll like receptor 4(HMGB1/TLR4)signaling pathway.Methods A rat model of AD was constructed,and AD rats were randomly divided into AD group,low-dose PA(PA-L)group,high-dose PA(PA-H)group,and high-dose PA+HMGB1 recombinant protein group(PA-H+r-HMGB1)group,with 24 rats per group.Another 24 normal rats were included in the control group.Enzyme-linked immunosorbent assay(ELISA)was applied to detect levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),and interleukin-10(IL-10)in rats.Hematoxylin and eosin(H&E)staining was applied to observe the pathological damage of rat hippocampal tissue.TUNEL staining was applied to detect apoptosis of rat hippocampal neurons.Immunohistochemistry was applied to observe the number of activated microglia in the hippocampus and the expression of β-amyloid 1-42(Aβ1-42)protein.Western blot was applied to detect protein expressions of proteins related to the HMGB1/TLR4 signaling pathway.Results Compared with those of the control group,rats in AD group suffered from severe neuronal loss or even degeneration and necrosis,nuclear pyknosis,disordered hippocampal tissue,obvious edema,significantly higher number of activated microglia,apoptotic rate of neurons,relative levels of TNF-α and IL-1β,and protein expressions of Bax,Aβ1-42,HMGB1,TLR4,p-NF-κB and p65/NF-κB p65,but lower level of IL-10 and protein expression of Bcl-2(P＜0.05).Compared with those of the AD group,rats in the PA-L and PA-H groups showed relieved neuronal loss,degeneration,necrosis,and nuclear pyknosis,relatively regular arrangement of hippocampal tissue,less edema,significantly lower number of activated microglia,apoptotic rate of neurons,relative levels of TNF-α andIL-1β,and protein expressions of Bax,Aβ1-42,HMGB1,TLR4,p-NF-κB and p65/NF-κB p65,but higher level of IL-10 and protein expression of Bcl-2(P＜0.05).The pathological degree of hippocampal tissue in rats of the PA-H+r-HMGB1 group was aggravated compared to those in the PA-H group,with significantly higher number of activated microglia,apoptotic rate of neurons,relative levels of TNF-α and IL-1 β,and protein expressions of Bax,Aβ1-42,HMGB1,TLR4,p-NF-κB and p65/NF-κB p65,but lower level of IL-10 and protein expression of Bcl-2(P＜0.05).Conclusion PA can improve neuroinflammation in AD rats by inhibiting the HMGB1/TLR4 signaling pathway.
Keywords：pachymic acidhigh mobility group box 1/Toll like receptor 4 signaling pathwayAlzheimer's diseaseneuroinflammation
Publication Date：2025-08-26
Online Publishing Date：2025-09-12(First online date of this platform, not the publication date of the document)
Pages：5( 1243-1247 )