Background:Acute respiratory distress syndrome(ARDS)is the major therapeutic dilemma associated with significant inflammation and severe pulmonary dysfunction.Liriodendrin is a bioactive compound extract from traditio...Background:Acute respiratory distress syndrome(ARDS)is the major therapeutic dilemma associated with significant inflammation and severe pulmonary dysfunction.Liriodendrin is a bioactive compound extract from traditional Chinesemedicine,historically utilized formodulating inflammatory responses and alleviating symptoms in multiple diseasemodels.Methods:At present,BALB/c mice to explore the effects of liriodendrin on lipopolysaccharide(LPS)-induced ARDS.Before LPS was administered,the mice were treated with either liriodendrin or dexamethasone.Leukocyte infiltration,lung edema,and alveolar-capillary barrier integrity were evaluated in the bronchoalveolar lavage fluid(BALF)and pulmonary parenchyma.The expression of adhesion molecules and proinflammatory cytokines in BALF was evaluated by enzyme-linked immunosorbent assay.Western blotting assay facilitated the analysis of the expression or phosphorylation of inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NOD-like receptor family pyrin domain-containing 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),cleaved caspase-1(CL-csapase-1),nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB),inhibitor of kappa B(IκB),mitogen-activated protein kinase(MAPK),and protein kinase B(Akt)in the lungs.In addition,the anti-inflammatory effects of liriodendrin were evaluated in LPS-stimulated RAW264.7 macrophages.Before LPS was administered,the RAW264.7 macrophages were treated with either liriodendrin or dexamethasone.Nitric Oxide(NO)production was measured using the Griess reaction assay,while ELISA assessed IL-1β,IL-6,and TNF-αlevels.Western blot analysis evaluated NF-κB phosphorylation and the expression of NLRP3,ASC,and CLcaspase-1.Results:These outcomes revealed that liriodendrin intervention markedly ameliorated the pathological features of LPS-induced ARDS,including leukocyte infiltration,lung edema,and alveolar-capillary barrier disruption.Liriodendrin also reduced the LPS-induced secretion of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesionmolecule-1(VCAM-1),expression of iNOS and COX2,and production of proinflammatory cytokines.Finally,we further discovered that the concentration trend of liriodendron amelioration ofARDSwas similar to those ofNLRP3 formation,NF-κB pathway activation,and p38 MAPK,c-Jun N-terminal kinase(JNK),and Akt phosphorylation but not to that of extracellular signal-regulated kinase(ERK)phosphorylation.Liriodendrin inhibited LPS-induced inflammatory responses in RAW264.7 macrophages.It markedly reduced NO production,propro-inflammatorytokines,NF-κB phosphorylation,and NLRP3 formation.Conclusions:In summary,liriodendrin effectively ameliorated the pathological features of LPS-induced ARDS inmice,demonstrating significant anti-inflammatory properties attributed to NLRP3 formation through NF-κB pathway activation by p38MAPK,JNK,and Akt phosphorylation.In LPS-treated RAW264.7 macrophages,liriodendrin reduced NO production,pro-inflammatory cytokines,and NLRP3 formation,suggesting its potential as an agent for ARDS and relative inflammation.展开更多
基金supported by Chung Shan Medical University and Changhua Christian Hospital(CSMU-CCH-111-08)supported by research grants from the Chung Shan Medical University Hospital,Taichung,Taiwan(CSH-2023-C-023)the National Science and Technology Council,Taiwan,for financially supporting this research under Contract Nos.NSTC 112-2320-B-040-017,NSTC112-2314-B-040-009,and NSTC 112-2320-B-040-011.
文摘Background:Acute respiratory distress syndrome(ARDS)is the major therapeutic dilemma associated with significant inflammation and severe pulmonary dysfunction.Liriodendrin is a bioactive compound extract from traditional Chinesemedicine,historically utilized formodulating inflammatory responses and alleviating symptoms in multiple diseasemodels.Methods:At present,BALB/c mice to explore the effects of liriodendrin on lipopolysaccharide(LPS)-induced ARDS.Before LPS was administered,the mice were treated with either liriodendrin or dexamethasone.Leukocyte infiltration,lung edema,and alveolar-capillary barrier integrity were evaluated in the bronchoalveolar lavage fluid(BALF)and pulmonary parenchyma.The expression of adhesion molecules and proinflammatory cytokines in BALF was evaluated by enzyme-linked immunosorbent assay.Western blotting assay facilitated the analysis of the expression or phosphorylation of inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NOD-like receptor family pyrin domain-containing 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),cleaved caspase-1(CL-csapase-1),nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB),inhibitor of kappa B(IκB),mitogen-activated protein kinase(MAPK),and protein kinase B(Akt)in the lungs.In addition,the anti-inflammatory effects of liriodendrin were evaluated in LPS-stimulated RAW264.7 macrophages.Before LPS was administered,the RAW264.7 macrophages were treated with either liriodendrin or dexamethasone.Nitric Oxide(NO)production was measured using the Griess reaction assay,while ELISA assessed IL-1β,IL-6,and TNF-αlevels.Western blot analysis evaluated NF-κB phosphorylation and the expression of NLRP3,ASC,and CLcaspase-1.Results:These outcomes revealed that liriodendrin intervention markedly ameliorated the pathological features of LPS-induced ARDS,including leukocyte infiltration,lung edema,and alveolar-capillary barrier disruption.Liriodendrin also reduced the LPS-induced secretion of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesionmolecule-1(VCAM-1),expression of iNOS and COX2,and production of proinflammatory cytokines.Finally,we further discovered that the concentration trend of liriodendron amelioration ofARDSwas similar to those ofNLRP3 formation,NF-κB pathway activation,and p38 MAPK,c-Jun N-terminal kinase(JNK),and Akt phosphorylation but not to that of extracellular signal-regulated kinase(ERK)phosphorylation.Liriodendrin inhibited LPS-induced inflammatory responses in RAW264.7 macrophages.It markedly reduced NO production,propro-inflammatorytokines,NF-κB phosphorylation,and NLRP3 formation.Conclusions:In summary,liriodendrin effectively ameliorated the pathological features of LPS-induced ARDS inmice,demonstrating significant anti-inflammatory properties attributed to NLRP3 formation through NF-κB pathway activation by p38MAPK,JNK,and Akt phosphorylation.In LPS-treated RAW264.7 macrophages,liriodendrin reduced NO production,pro-inflammatory cytokines,and NLRP3 formation,suggesting its potential as an agent for ARDS and relative inflammation.
