南京中医药大学学报2025，Vol.41Issue(3)：341-351,11.DOI:10.14148/j.issn.1672-0482.2025.0341
没食子酸靶向β-arrestin2抑制星形胶质细胞炎症的机制研究
Mechanism Study of Gallic Acid Targeting β-arrestin2 to Inhibit Astrocyte Inflammation
摘要
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.关键词
β-arrestin2/没食子酸/星形胶质细胞/神经炎症/NF-κB信号通路/NLRP3炎症小体Key words
β-arrestin2/gallic acid/astrocytes/neuroinflammation/NF-κB signaling pathway/NLRP3 inflammasome分类
医药卫生引用本文复制引用
夏行宇,王东硕,林彬燕,朱琴..没食子酸靶向β-arrestin2抑制星形胶质细胞炎症的机制研究[J].南京中医药大学学报,2025,41(3):341-351,11.基金项目
江苏省高等学校基础科学(自然科学)面上项目(21KJB360015) （自然科学）
