Vanillin Modulates M1/M2 Microglial Polarization in Parkinson's Disease via the SIRT1/NF-κB Signaling Pathway
GAO Yuan
PENG Jiaxin
LONG Jingjing
LI Shulin
MENG Qiang
Abstract：Objective This study aims to explore whether vanillin alleviates neuroinflammation and protects dopaminergic neurons in a Parkinson's disease(PD)model by regulating the M1/M2 polarization balance of microglia through activation of the silent information regulator 1/nuclear factor-κB(SIRT1/NF-κB)pathway.Methods Forty male C57BL/6 mice were randomly divided into a control group,an MPTP group,an MPTP+low-dose vanillin group,and an MPTP+high-dose vanillin group to establish an MPTP-induced PD model,each group n=10.In vitro,LPS was used to stimulate BV2 microglial cells,which were divided into a control group,an LPS group,an LPS+vanillin(50 μmol/L)group,an LPS+vanillin(100 μmol/L)group,and an LPS+vanillin(100 μmol/L)+EX527 group.Motor function was evaluated using behavioral tests(rotarod and pole tests).Immunohistochemistry was used to detect TH+neurons in the substantia nigra.Immunofluorescence,enzyme-linked immunosorbent assay(ELISA),real-time quantitative polymerase chain reaction(qPCR),and Western blot were employed to assess microglial polarization phenotypes,inflammatory cytokine levels,and pathway-related protein expression.Results Compared with the control group,the MPTP group showed a significant decrease in the retention time on the rotarod test[(92.3±8.7)s vs(180.5±10.2)s,P<0.05]and an increase in the total time in the pole test[(12.8±1.5)s vs(5.2±0.8)s,P<0.05].Compared with the MPTP group,both vanillin treatment groups showed significant improvement in these behavioral indicators(P<0.05).The MPTP group exhibited a decrease in the number of TH+neurons,TH protein,CD206+cells,and expression of Arg-1 and SIRT1 protein,while iNOS+cells,iNOS protein,and the p-p65/p65 ratio were significantly increased(P<0.05).Vanillin treatment reversed these changes(P<0.05).In LPS-stimulated BV2 cells,levels of TNF-α,IL-1β,iNOS mRNA and protein,and the p-p65/p65 ratio were significantly elevated,while IL-10,Arg-1 mRNA and protein,and SIRT1 protein expression were decreased(P<0.05).Vanillin treatment dose-dependently reversed these indicators(P<0.05).EX527 antagonized the effects of vanillin,leading to increased p-p65/p65 ratio,TNF-α and IL-1β levels,and decreased Arg-1 expression(P<0.05).Conclusion Vanillin promotes the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype by activating the SIRT1/NF-κB signaling pathway,thereby alleviating neuroinflammation and exerting neuroprotective effects.
Keywords：Parkinson's diseasevanillinmicroglia polarizationsilent information regulator 1nuclear factor kappa Bneuroinflammation
Publication Date：2025-10-20
Online Publishing Date：2025-10-28(First online date of this platform, not the publication date of the document)
Pages：7( 137-143 )