Mechanism Study of Gallic Acid Targeting β-arrestin2 to Inhibit Astrocyte Inflammation
10.14148/j.issn.1672-0482.2025.0341
- VernacularTitle:没食子酸靶向β-arrestin2抑制星形胶质细胞炎症的机制研究
- Author:
Xingyu XIA
1
;
Dongshuo WANG
;
Binyan LIN
;
Qin ZHU
Author Information
1. 南京中医药大学药学院,江苏 南京 210023
- Publication Type:Journal Article
- Keywords:
β-arrestin2;
gallic acid;
astrocytes;
neuroinflammation;
NF-κB signaling pathway;
NLRP3 inflammasome
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2025;41(3):341-351
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the mechanism of gallic acid targeting β-arrestin2 to inhibit astrocyte inflammation.METHODS Potential targets of gallic acid were found by PharmMapper and verified by thermal shift and molecular docking experi-ments.Western blot was used to detect the expression of β-arrestin2,NF-κB signaling pathway and NLRP3 inflammasome-related proteins;qPCR was used to detect the mRNA levels of proinflammatory cytokines such as IL-1β,IL-6 and TNF-α.A subacute PD mouse model induced by MPTP was established,and the behavioral ability of mice was evaluated by open field test,rotating rod test and climbing pole test;the number of TH+and GFAP+cells in the SNc area of mice was detected by immunohistochemistry;Western blot was used to detect the expression of NF-κB signaling pathway and NLRP3 inflammasome-related proteins in the homogenate pro-tein of mouse midbrain tissue.RESULTS Molecular docking experiments and thermal shift experiments showed that gallic acid could directly bind to β-arrestin2.Gallic acid could reduce the expression of p-IKK and p-P65 proteins in astrocytes(P<0.001,P<0.000 1),reduce the mRNA levels of IL-1β,IL-6 and TNF-α(P<0.05,P<0.01),and reduce the expression of caspase-1 and IL-1β proteins(P<0.000 1),but had no effect on the expression of β-arrestin2 protein(P>0.05).Gallic acid could improve the be-havioral ability of PD model mice,increase the number of TH+neurons and GFAP+cells in PD model mice(P<0.05,P<0.001),and reduce the expression of caspase-1,IL-1β,NLRP3 and p-IKK proteins in the brain of PD model mice(P<0.05).CONCLU-SION Gallic acid inhibits the activation of NF-κB signaling pathway and NLRP3 inflammasome by binding to β-arrestin2 to reduce astrocyte inflammation,and has a neuroprotective effect on MPTP-induced PD model mice.
