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
Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viabilit...Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viability was processed when treated with 50 μmol·L^-1 of dopamine for 24 h by MTT assay. Early apoptosis, late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide （PI） double-staining, respectively. Generation of reactive oxygen species （ROS） was assessed by DCFH-DA, an oxidation-sensitive fluorescent probe. To evaluate mitochondrion membrane potential （Δψm） using flow cytometry with the fluorescent dye Rhodamine 123. The transcriptional level of P53 was studied using RT- PCR. Results The dopamine-induced loss of cell viability was significantly attenuated by liriodendrin treatment at the concentration of 10^-8, 10^-7, 10^-6, 10^-5 and 10^-4 mol·L^-1. The protective effects of liriodendrin （10^-7, 10^-6 and 10^-5 mol·L^-1） on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing ROS level and anti-apoptotic effect via protection of Δψm. In addition, the effect of liriodendrin may involve the P53 pathway in apoptosis. Conclusion Liriodendrin may provide a useful therapeutic strategy for the treatment of neurodegenerative diseases such as Parkinson＇s disease （PD）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National Natural Sciences Foundation of China(Grant No.30370720and No.30572343)Nationa l973 Fundamental Project of China(No.2004CB518906)
文摘Aim To investigate the effect of liriodendrin, an extract from Fraxinus sielboldiana blume belonging to the Oleaceae family, on dopamine-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Methods Cell viability was processed when treated with 50 μmol·L^-1 of dopamine for 24 h by MTT assay. Early apoptosis, late apoptosis/necrosis were analyzed by flow cytometry using Annexin V-FITC and propidium iodide （PI） double-staining, respectively. Generation of reactive oxygen species （ROS） was assessed by DCFH-DA, an oxidation-sensitive fluorescent probe. To evaluate mitochondrion membrane potential （Δψm） using flow cytometry with the fluorescent dye Rhodamine 123. The transcriptional level of P53 was studied using RT- PCR. Results The dopamine-induced loss of cell viability was significantly attenuated by liriodendrin treatment at the concentration of 10^-8, 10^-7, 10^-6, 10^-5 and 10^-4 mol·L^-1. The protective effects of liriodendrin （10^-7, 10^-6 and 10^-5 mol·L^-1） on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing ROS level and anti-apoptotic effect via protection of Δψm. In addition, the effect of liriodendrin may involve the P53 pathway in apoptosis. Conclusion Liriodendrin may provide a useful therapeutic strategy for the treatment of neurodegenerative diseases such as Parkinson＇s disease （PD）
基金co-financed by the grants from the Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin of Xinjiang,China(BRZD1102)The Hi-Tech R&D Program of China(2011AA10A202)
