Effect of phloretin on inflammatory response in acute lung injury rats by regulating the IL-6/JAK2/STAT3 signaling pathway
JIA Zhiyong
QI Yao
LI Mingfu
Abstract：Objective To investigate the effect of phloretin on inflammatory response in acute lung injury(ALI)rats by regulating the interleukin-6(IL-6)/tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods A total of 60 Sprague-Dawley(SD)rats in the specific pathogen free(SPF)levels were randomly assigned into ALI group,control group,phloretin group,recombinant rat IL-6 protein(rRIL-6)group,and Phloretin+rRIL-6 group,with 12 rats in each group.Except for those in the control group,rats in the remaining groups were subjected to ALI modeling by intratracheal instillation of lipopolysaccharide(LPS).After successful modeling,they were immediately administered once a day for 2 weeks.Lung function changes in peak inspiratory flow rate(PIF),minute ventilation(MV),and peak expiratory flow rate(PEF)were detected.Flow cytometry was applied to detect changes in CD86+M1 macrophages and CD206+M2 macrophages in alveoli.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of IL-10,arginase 1(Arg-1),and interferon-γ(IFN-γ)in bronchoalveolar lavage fluid(BALF).The wet-to-dry weight ratio of lung tissue was detected.The hematoxylin and eosin(H&E)staining was applied to detect pathological changes in lung tissue.Western blot was applied to detect protein levels of p-JAK2,IL-6,and p-STAT3 in lung tissue.Results Compared with those of the control group,rats in the ALI group presented pathological damage in lung tissue like infiltration of inflammatory cells,thickening of alveolar walls,and destruction of alveoli,significantly lower PIF,MV,PEF,IL-10 and Arg-1 levels in BALF and CD206+M2 macrophages,but higher CD86+M1 macrophages in the alveoli,IFN-γ,wet-to-dry weight ratio of lung tissue,and protein expressions of p-JAK2,IL-6,and p-STAT3 in BALF(P＜0.05).Compared with those of the ALI group,rats in the phloretin group showed less pathological damage to lung tissue,significantly higher PIF,MV,PEF,IL-10 and Arg-1 levels in BALF and CD206+M2 macrophages,but lower CD86+M1 macrophages in the alveoli,IFN-γ,wet-to-dry weight ratio of lung tissue,and protein expressions of p-JAK2,IL-6,and p-STAT3 in BALF(P＜0.05).Rats in the rRIL-6 group showed opposite trends in the above data than those of phloretin group(P＜0.05).The treatment of rRIL-6 weakened the inhibitory effect of phloretin on inflammatory response in ALI rats and its improvement effects on pulmonary edema and lung injury.Conclusion Phloretin inhibits inflammatory response,pulmonary edema,and lung injury in ALI rats by blocking the IL-6/JAK2/STAT3 pathway.
Keywords：phloretinacute lung injuryinflammationinterleukin-6/tyrosine kinase 2/signal transducer and activator of transcription 3 pathway
Publication Date：2025-04-26
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 546-550 )