DOI: 10.1002/ame2.70100
Polydatin alleviates mitochondrial damage and apoptosis of lung epithelial cells by inhibiting toll-like receptor 4-dependent macrophage activation in asthma
Guangxing Li1
Ruobai Liu1
Chang Xu1
Jianing Yang1
Yilan Song1
Li Li1
Jingzhi Jiang1
Liangchang Li1
Chongyang Wang2
Guanghai Yan2
1.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.China2.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.China;Key Laboratory of Natural Medicines of the Changbai Mountain,Ministry of Education,Yanbian University,Yanji,P.R.China
摘要：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 40mg/kg)were evaluated in this asthmatic mouse model.To assess the underlying mechanisms,Bronchial Epithelium Adenovirus 12-SV40 2B(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-1β and 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-1β and 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.
机标关键词：apoptosisreceptortoll-likecellsdamage4-dependentactivationalleviates
论文发表日期：2026-01-30
在线出版日期：2026-03-27（本平台首次上网日期，不代表文献的发表时间）
页数：14( 89-102 )
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