scholarly journals Bergamottin alleviates LPS-induced acute lung injury by inducing SIRT1 and suppressing NF-κB

2021 ◽  
pp. 175342592110625
Author(s):  
Ning An ◽  
Tao Yang ◽  
Xiao-Xia Zhang ◽  
Mei-xia Xu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
In Vivo Studies ◽  
Lung Edema ◽  
Monocyte Chemoattractant Protein 1 ◽  
Mouse Macrophages ◽  
Anti Inflammatory ◽  
Pre Treatment

Acute lung injury (ALI) is associated with a high mortality due to inflammatory cell infiltration and lung edema. The development of ALI commonly involves the activation of NF-κB. Since bergamottin is a natural furanocoumarin showing the ability to inhibit the activation of NF-κB, in this study we aimed to determine the effect of bergamottin on ALI. RAW264.7 mouse macrophages were pre-treated with bergamottin and then stimulated with LPS. Macrophage inflammatory responses were examined. Bergamottin (50 mg/kg body mass) was intraperitoneally administrated to mice 12 h before injection of LPS, and the effect of bergamottin on LPS-induced ALI was evaluated. Our results showed that LPS exposure led to increased production of TNF-α, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which was impaired by bergamottin pre-treatment. In vivo studies confirmed that bergamottin pre-treatment suppressed LPS-induced lung inflammation and edema and reduced the levels of pro-inflammatory cytokines in lung tissues and bronchoalveolar lavage fluids. Mechanistically, bergamottin blocked LPS-induced activation of NF-κB signaling in lung tissues. Additionally, bergamottin treatment reduced NF-κB p65 protein acetylation, which was coupled with induction of SIRT1 expression. In conclusion, our results reveal the anti-inflammatory property of bergamottin in preventing ALI. Induction of SIRT1 and inhibition of NF-κB underlies the anti-inflammatory activity of bergamottin.

scholarly journals Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seongchan Kim ◽  
Shin Young Kim ◽  
Seung Joon Rho ◽  
Seung Hoon Kim ◽  
So Hyang Song ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Intratracheal Instillation ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

Protective effect of hydrogen sulfide in a murine model of acute lung injury induced by combined burn and smoke inhalation

2008 ◽  
Vol 115 (3) ◽  
pp. 91-97 ◽  
Author(s):  
Aimalohi Esechie ◽  
Levente Kiss ◽  
Gabor Olah ◽  
Eszter M. Horváth ◽  
Hal Hawkins ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Murine Model ◽  
Smoke Inhalation ◽  
In Vivo Studies ◽  
Protective Effects ◽  
Pulmonary Endothelium ◽  
Anti Inflammatory

Acute lung injury results in a severe inflammatory response, which leads to priming and activation of leucocytes, release of reactive oxygen and reactive nitrogen species, destruction of pulmonary endothelium, extravasation of protein-rich fluid into the interstitium and formation of oedema. Recently, H2S (hydrogen sulfide) has been shown to decrease the synthesis of pro-inflammatory cytokines, reduce leucocyte adherence to the endothelium and subsequent diapedesis of these cells from the microvasculature in in vivo studies, and to protect cells in culture from oxidative injury. In the present study, we hypothesized that a parenteral formulation of H2S would reduce the lung injury induced by burn and smoke inhalation in a novel murine model. H2S post-treatment significantly decreased mortality and increased median survival in mice. H2S also inhibited IL (interleukin)-1β levels and significantly increased the concentration of the anti-inflammatory cytokine IL-10 in lung tissue. Additionally, H2S administration attenuated protein oxidation following injury and improved the histological condition of the lung. In conclusion, these results suggest that H2S exerts protective effects in acute lung injury, at least in part through the activation of anti-inflammatory and antioxidant pathways.

scholarly journals Tanreqing Inhibits LPS-Induced Acute Lung Injury In Vivo and In Vitro Through Downregulating STING Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-Qiong He ◽  
Can-Can Zhou ◽  
Jiu-Ling Deng ◽  
Liang Wang ◽  
Wan-Sheng Chen
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Lung Edema ◽  
Protective Effects ◽  
And Oxidative Stress

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

scholarly journals Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6073
Author(s):  
Laily Rahmawati ◽  
Nur Aziz ◽  
Jieun Oh ◽  
Yo Han Hong ◽  
Byoung Young Woo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Raw264.7 Cells ◽  
Acute Gastritis ◽  
Anti Inflammatory

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.

The therapeutic effect of Bletilla striata extracts on LPS-induced acute lung injury by regulation of inflammation and oxidation

RSC Advances ◽  
2016 ◽  
Vol 6 (92) ◽  
pp. 89338-89346 ◽  
Author(s):  
Yongjie Wang ◽  
Weizhen Huang ◽  
Jiaozhen Zhang ◽  
Min Yang ◽  
Qiuchen Qi ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Effect ◽  
Inflammatory Responses ◽  
Active Ingredients ◽  
Bletilla Striata ◽  
Anti Inflammatory

Identification of active ingredients, and their structures, from Bletilla striata and investigation of the antioxidative and anti-inflammatory responses in vitro and in vivo.

scholarly journals Celastrol alleviates LPS-induced inflammation in BMDMs and acute lung injury in mice via inhibition of p-38 MAPK/MK2 signaling

2021 ◽  
Vol 19 ◽  
pp. 205873922110205
Author(s):  
Zhengxu Chen ◽  
Xinyi Yang ◽  
Lu Zhang ◽  
Man Li ◽  
Lei Sun ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
P38 Mapk ◽  
Lavage Fluid ◽  
Lung Edema ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Objective: Celastrol is a compound extracted from a medicinal plant Tripterygium wilfordii which has a broad-spectrum anti-inflammatory effect in traditional medicine. However, the effect of celastrol on acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is still unknown. Methods: We reported that celastrol alleviated LPS-induced acute lung injury by H&E staining, MPO activity and the expression of cytokines in broncho-alveolar lavage fluid. The effect of celastrol on bone marrow-derived macrophages (BMDMs) after LPS treatment was measured by ELISA and Western blotting. Results: In vivo, celastrol reduced the LPS-induced lung edema and MPO activity of lung tissue. Furthermore, the production of inflammatory cytokines IL-6, TNF-α, and KC in bronchoalveolar lavage was reduced. In vitro, upon treatment of LPS, celastrol dose-dependently inhibited the expression of iNOS in BMDMs. Meanwhile, the expression of IL-6, TNF-α, and KC in BMDMs were also inhibited by celastrol treatment. Furthermore, we found that celastrol attenuated the phosphorylation of p38 MAPK and MK2, and inhibited the interaction between p38 MAPK and MK2. Conclusion: Our data indicate that celastrol has an anti-inflammatory effect on LPS-induced inflammatory response in vivo and in vitro, suggesting celastrol is a promising compound for the treatment of ALI and ARDS.

scholarly journals Substrate stiffness-dependent exacerbation of endothelial permeability and inflammation: mechanisms and potential implications in ALI and PH (2017 Grover Conference Series)

2018 ◽  
Vol 8 (2) ◽  
pp. 204589401877304 ◽  
Author(s):  
Pratap Karki ◽  
Anna A. Birukova
Keyword(s):  
Lung Injury ◽  
Inflammatory Responses ◽  
Mechanical Strain ◽  
Endothelial Permeability ◽  
Endothelial Barrier ◽  
In Vivo Studies ◽  
Potential Implication ◽  
Vascular Stiffening ◽  
Life Threatening

The maintenance of endothelial barrier integrity is absolutely essential to prevent the vascular leak associated with pneumonia, pulmonary edema resulting from inhalation of toxins, acute elevation to high altitude, traumatic and septic lung injury, acute lung injury (ALI), and its life-threatening complication, acute respiratory distress syndrome (ARDS). In addition to the long-known edemagenic and inflammatory agonists, emerging evidences suggest that factors of endothelial cell (EC) mechanical microenvironment such as blood flow, mechanical strain of the vessel, or extracellular matrix stiffness also play an essential role in the control of endothelial permeability and inflammation. Recent studies from our group and others have demonstrated that substrate stiffening causes endothelial barrier disruption and renders EC more susceptible to agonist-induced cytoskeletal rearrangement and inflammation. Further in vivo studies have provided direct evidence that proinflammatory stimuli increase lung microvascular stiffness which in turn exacerbates endothelial permeability and inflammation and perpetuates a vicious circle of lung inflammation. Accumulating evidence suggests a key role for RhoA GTPases signaling in stiffness-dependent mechanotransduction mechanisms defining EC permeability and inflammatory responses. Vascular stiffening is also known to be a key contributor to other cardiovascular diseases such as arterial pulmonary hypertension (PH), although the precise role of stiffness in the development and progression of PH remains to be elucidated. This review summarizes the current understanding of stiffness-dependent regulation of pulmonary EC permeability and inflammation, and discusses potential implication of pulmonary vascular stiffness alterations at macro- and microscale in development and modulation of ALI and PH.

scholarly journals Anemoside B4 Protects against Acute Lung Injury by Attenuating Inflammation through Blocking NLRP3 Inflammasome Activation and TLR4 Dimerization

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Renyikun Yuan ◽  
Jia He ◽  
Liting Huang ◽  
Li-Jun Du ◽  
Hongwei Gao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Macrophage Cells ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

Acute lung injury (ALI) is an acute inflammatory process in the lung parenchyma. Anemoside B4 (B4) was isolated from Pulsatilla, a plant-based drug against inflammation and commonly applied in traditional Chinese medicine. However, the anti-inflammatory effect and the mechanisms of B4 are not clear. In this study, we explored the potential mechanisms and anti-inflammatory activity of B4 both in vitro and in vivo. The results indicated that B4 suppressed the expression of iNOS, COX-2, NLRP3, caspase-1, and IL-1β. The ELISA assay results showed that B4 significantly restrained the release of inflammatory cytokines like TNF-α, IL-6, and IL-1β in macrophage cells. In addition, B4 rescued mitochondrial membrane potential (MMP) loss in (lipopolysaccharide) LPS plus ATP stimulated macrophage cells. Co-IP and molecular docking results illustrated that B4 disrupted the dimerization of TLR4. For in vivo results, B4 exhibited a protective effect on LPS and bleomycin- (BLM-) induced ALI in mice through suppressing the lesions of lung tissues, the release of inflammatory cytokines, and the levels of white blood cells, neutrophils, and lymphoid cells in the blood. Collectively, B4 has a protective effect on ALI via blocking TLR4 dimerization and NLRP3 inflammasome activation, suggesting that B4 is a potential agent for the treatment of ALI.

scholarly journals Osthole Protects against Acute Lung Injury by Suppressing NF-κB-Dependent Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yiyi Jin ◽  
Jianchang Qian ◽  
Xin Ju ◽  
Xiaodong Bao ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Nuclear Translocation ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Peritoneal Macrophages ◽  
Anti Inflammatory

Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.

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