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
Objective:This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury(SCI)in the central nervous system(CNS)and its mechanism in promoting the structural and functional reco...Objective:This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury(SCI)in the central nervous system(CNS)and its mechanism in promoting the structural and functional recovery of the injured CNS.Methods:A compressive SCI mouse model was utilized for this investigation.Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein,acrolein-induced inflammation-related factors,and macrophages at the injury site and within the CNS.Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase(PI3K)/AKT pathway to study macrophage regulation.The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67(GAD65/67),vesicular glutamate transporter 1(VGLUT1),paw withdrawal response,and Basso Mouse Scale score.Nissl staining and Luxol Fast Blue(LFB)staining were performed to investigate the structural recovery of the injured CNS.Results:Hydralazine downregulated the levels of acrolein,IL-1β,and TNF-αin the spinal cord.The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway,leading to M2 macrophage polarization,which protected neurons against SCI-induced inflammation.Additionally,hydralazine promoted the structural recovery of the injured spinal cord area.Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression.Furthermore,hydralazine facilitated motor function recovery following SCI.Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.Conclusion:Hydralazine,an acrolein scavenger,significantly mitigated SCI-induced inflammation and oxidative stress in vivo,modulated macrophage activation,and consequently promoted the structural and functional recovery of the injured CNS.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.
基金supported by the National Natural Science Foundation of China Young Scientists Fund(No.81801216,No.81802143,No.81901966)the China Postdoctoral Foundation(No.2018M633748).
文摘Objective:This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury(SCI)in the central nervous system(CNS)and its mechanism in promoting the structural and functional recovery of the injured CNS.Methods:A compressive SCI mouse model was utilized for this investigation.Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein,acrolein-induced inflammation-related factors,and macrophages at the injury site and within the CNS.Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase(PI3K)/AKT pathway to study macrophage regulation.The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67(GAD65/67),vesicular glutamate transporter 1(VGLUT1),paw withdrawal response,and Basso Mouse Scale score.Nissl staining and Luxol Fast Blue(LFB)staining were performed to investigate the structural recovery of the injured CNS.Results:Hydralazine downregulated the levels of acrolein,IL-1β,and TNF-αin the spinal cord.The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway,leading to M2 macrophage polarization,which protected neurons against SCI-induced inflammation.Additionally,hydralazine promoted the structural recovery of the injured spinal cord area.Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression.Furthermore,hydralazine facilitated motor function recovery following SCI.Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.Conclusion:Hydralazine,an acrolein scavenger,significantly mitigated SCI-induced inflammation and oxidative stress in vivo,modulated macrophage activation,and consequently promoted the structural and functional recovery of the injured CNS.
