Glycyrrhetinic acid promotes LPS-induced M2 polarization of microglia by inhibiting p38 mitogen-activated protein kinase signaling pathway
Zhang Mengmeng
Yin Tao
Wang Ruijian
Zhang Wenchao
Abstract：Objective To explore the effect of glycyrrhetinic acid(GA)on lipopolysaccharide(LPS)-induced M2 polarization of microglia by inhibiting p38 mitogen-activated protein kinase(p38 MAPK)signaling pathway.Methods Murine microglial BV2 cells were divided into negative control(NC)group,LPS group(100 μg/ml),GA group(100 μg/ml LPS+10 μmol/L GA),GA+inhibitor group(100 μg/ml LPS+10 μmol/L GA+10 μmol/ml p38 MAPK pathway inhibitor),inhibitor group(100 μg/ml LPS+10 μmol/ml p38 MAPK pathway inhibitor)and GA+activator group(100 μg/mL LPS+10 μmol/L GA+300 ng/ml P38 MAPK pathway activator).CCK-8 as-say was used to measure cell viability,ELISA to determine inflammatory factor levels,inverted microscopy to observe cell morphology,and Western blotting to detect the protein levels of argi-nase 1(Arg-1),inducible nitric oxide synthase(iNOS)and p38-MAPK pathway-related proteins.Results Compared with the LPS group,more microglial processes,enlarged cell bodies and re-duced intercellular space,decreased levels of IL-1β and IL-6,and reduced protein levels of iNOS,p53 and p-p38 MAPK(22.53±0.53 and 24.13±1.00 vs 29.56±1.46,10.37±0.59 and 10.16±0.21 vs 15.13±1.00,0.39±0.01 and 0.38±0.01 vs 1.12±0.01,0.34±0.01 and 0.31±0.01 vs 0.89± 0.01,0.40±0.01 and 0.40±0.02 vs 0.88±0.01,P＜0.05),while increased IL-10 level and Arg-1 expression(177.33±7.57 and 187.21±6.87 vs 64.67±11.50,0.41±0.01 and 0.44±0.03 vs 0.10± 0.01,P＜0.05)were observed in the GA group and the inhibitor group.The GA+inhibitor group showed more microglial processes,enlarged cell bodies,reduced IL-1β and IL-6 levels and iNOS,p53 and p-p38 MAPK levels,and increased IL-10 level and Arg-1 expression when compared with the GA group(P＜0.05).Moreover,opposite phenomena were observed in the GA+activator group(P＜0.05).Conclusion GA can promote LPS-induced M2 polarization of murine microglial BV2 cells by blocking the p38 MAPK signaling pathway.
Keywords：glycyrrhetinic acidp38 mitogen-activated protein kinaseslipopolysaccharidesmicroglia
Publication Date：2024-04-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 450-454 )