Polydatin alleviates mitochondrial damage and apoptosis of lung epithelial cells by inhibiting toll-like receptor 4-dependent macrophage activation in asthmaOA
Background:This study investigated the role of polydatin in regulating macrophage-epithelial cell(EC)interactions during asthma.An asthma model was induced in BALB/c mice using ovalbumin(20μg).Methods:The therapeutic effects of polydatin(20 and 40 mg/kg)were evaluated in this asthmatic mouse model.To assess the underlying mechanisms,Bronchial Epithelium Adenovirus 12-SV402B(BEAS-2B)cells were cocultured with Tohoku Hospital for Pediatrics-1(THP-1)macrophages,in which toll-like receptor 4(TLR4)was either overexpressed or knocked down,and subsequently stimulated with lipopoly-saccharide(LPS)and ATP.THP-1 cells underwent a 1-h pretreatment with polydatin(50 and 100μmol/L),Class Lipid Inhibitor-095(CLI-095,TLR4 inhibitor,1μg/mL),or A438079(P2X7R antagonist,10μmol/L)prior to LPS/ATP challenge.Results:Findings from Western blotting,enzyme-linked immunosorbent assay,flow cytometry,real-time polymerase chain reaction,and immunofluorescence assays demonstrated that modulating TLR4 expression significantly altered interleukin-1β(IL-1β)secretion from THP-1 macrophages and mitochondrial reactive oxygen species(mtROS)production in BEAS-2B ECs.In the mouse asthma model,polydatin significantly alleviated airway inflammation,oxidative stress,and apoptosis,likely by interfering with TLR4/P2X7R-mediated signaling and suppressing the activation of the NOD-like receptor protein inflammasome.Additionally,polydatin significantly reduced IL-1βand IL-18 levels and inhibited the infiltration of macrophages and eosinophils.Correspondingly,polydatin significantly attenuated TLR4/P2X7R signaling in THP-1 cells stimulated with ATP and LPS,thereby reducing IL-1βand IL-18 secretion,calcium influx,mtROS production,and apoptosis in BEAS-2B ECs.Conclusions:Polydatin is a promising therapeutic candidate for asthma,possibly by targeting macrophage-epithelium cross-talk via the TLR4/P2X7R axis.Future formulations as capsules or sprays may effectively alleviate airway inflammation and remodeling.
Guangxing Li;Ruobai Liu;Chang Xu;Jianing Yang;Yilan Song;Li Li;Jingzhi Jiang;Liangchang Li;Chongyang Wang;Guanghai Yan
Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.China Key Laboratory of Natural Medicines of the Changbai Mountain,Ministry of Education,Yanbian University,Yanji,P.R.ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases,Yanbian University,Yanji,P.R.China Department of Anatomy,Histology and Embryology,Yanbian University Medical College,Yanji,P.R.China Key Laboratory of Natural Medicines of the Changbai Mountain,Ministry of Education,Yanbian University,Yanji,P.R.China
医药卫生
cell-cell cross-talkNOD-like receptor protein(NLRP3)inflammasomeovalbumin(OVA)stimulationtoll-like receptor 4(TLR4)/P2X7R synergy
《Animal Models and Experimental Medicine》 2026 (1)
P.89-102,14
National Natural Science Foundation of China,Grant/Award Number:82260007Jilin Province Health Commission,Grant/Award Number:2024A062Jilin Provincial Department of Education,Grant/Award Number:JJKH20240698KJJilin Province Science and Technology Department,Grant/Award Number:20240404025ZP and 20240602100RC。
评论