scholarly journals Nerolidol Suppresses the Inflammatory Response during Lipopolysaccharide-Induced Acute Lung Injury via the Modulation of Antioxidant Enzymes and the AMPK/Nrf-2/HO-1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yung-Lun Ni ◽  
Huan-Ting Shen ◽  
Chun-Hung Su ◽  
Wen-Ying Chen ◽  
Rosa Huang-Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Rapid Onset ◽  
Lung Edema ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Anticancer Properties ◽  
Life Threatening

Acute lung injury (ALI) is a life-threatening disease that is characterised by the rapid onset of inflammatory responses. Lipopolysaccharide (LPS) is an endotoxin that plays an important role in triggering ALI via pneumonia and sepsis. However, no effective therapeutic strategies are currently available to treat ALI. Nerolidol is an aliphatic sesquiterpene alcohol that is found in the essential oils of many flowers as well as floral plants. It has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Herein, we show that nerolidol pretreatment counteracted the histopathological hallmarks in LPS-induced ALI mice. Indeed, nerolidol pretreatment inhibited LPS-induced alveolar-capillary barrier disruption, lung edema, and lipid peroxidation. Moreover, nerolidol pretreatment prevented the LPS from decreasing the enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase. Importantly, nerolidol treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Taken together, our study reveals the novel protective effects of nerolidol in LPS-induced ALI via the induction of antioxidant responses and activation of the AMPK/Nrf-2/HO-1 signalling pathway.

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 Pterostilbene 4′-β-Glucoside Attenuates LPS-Induced Acute Lung Injury via Induction of Heme Oxygenase-1

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Jeongmin Park ◽  
Yingqing Chen ◽  
Min Zheng ◽  
Jinhyun Ryu ◽  
Gyeong Jae Cho ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mouse Lung ◽  
Heme Oxygenase 1 ◽  
Ros Production ◽  
Protective Effects ◽  
Anti Inflammatory

Heme oxygenase-1 (HO-1) can exert anti-inflammatory and antioxidant effects. Acute lung injury (ALI) is associated with increased inflammation and influx of proinflammatory cells and mediators in the airspaces and lung parenchyma. In this study, we demonstrate that pterostilbene 4′-β-glucoside (4-PG), the glycosylated form of the antioxidant pterostilbene (PTER), can protect against lipopolysaccharide- (LPS-) orPseudomonas aeruginosa- (P. aeruginosa-) induced ALI when applied as a pretreatment or therapeutic post-treatment, via the induction of HO-1. To determine whether HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG, we subjected mice genetically deficient inHmox-1to LPS-induced ALI and evaluated histological changes, HO-1 expression, and proinflammatory cytokine levels in bronchoalveolar lavage (BAL) fluid. 4-PG exhibited protective effects on LPS- orP. aeruginosa-induced ALI by ameliorating pathological changes in lung tissue and decreasing proinflammatory cytokines. In addition, HO-1 expression was significantly increased by 4-PG in cells and in mouse lung tissues. The glycosylated form of pterostilbene (4-PG) was more effective than PTER in inducing HO-1 expression. Genetic deletion ofHmox-1abolished the protective effects of 4-PG against LPS-induced inflammatory responses. Furthermore, we found that 4-PG decreased both intracellular ROS levels and mitochondrial (mt) ROS production in a manner dependent on HO-1. Pharmacological application of the HO-1 reaction product carbon monoxide (CO), but not biliverdin or iron, conferred protection inHmox-1-deficient macrophages. Taken together, these results demonstrate that 4-PG can increase HO-1 expression, which plays a critical role in ameliorating intracellular and mitochondrial ROS production, as well as in downregulating inflammatory responses induced by LPS. Therefore, these findings strongly suggest that HO-1 mediates the antioxidant and anti-inflammatory effects of 4-PG.

scholarly journals The Protective Effect of Alpha-Lipoic Acid in Lipopolysaccharide-Induced Acute Lung Injury Is Mediated by Heme Oxygenase-1

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Yu-Chieh Lin ◽  
Yuan-Shu Lai ◽  
Tz-Chong Chou
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Lipoic Acid ◽  
Inflammatory Responses ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Myeloperoxidase Activity ◽  
Nuclear Factor ◽  
Alpha Lipoic Acid

Alpha-lipoic acid (ALA), occurring naturally in human food, is known to possess antioxidative and anti-inflammatory activities. Induction of heme oxygenase-1 (HO-1) has been reported to exhibit a therapeutic effect in several inflammatory diseases. The aim of study was to test the hypothesis that the protection of ALA against lipopolysaccharide-(LPS-) induced acute lung injury (ALI) is mediated by HO-1. Pre- or posttreatment with ALA significantly inhibited LPS-induced histological alterations of ALI, lung tissue edema, and production of proinflammatory cytokine, cytokine inducible neutrophil chemoattractant-3, and nitrite/nitrate in bronchoalveolar lavage fluid. In addition, the inflammatory responses including elevation of superoxide formation, myeloperoxidase activity, polymorphonuclear neutrophils infiltration, nitrotyrosine, inducible nitric oxide synthase expression and nuclear factor-kappa B (NF-κB) activation in lung tissues of LPS-instilled rats were also markedly reduced by ALA. Interestingly, treatment with ALA significantly increased nuclear factor-erythroid 2-related factor 2 (Nrf2) activation and HO-1 expression in lungs of ALI. However, blocking HO-1 activity by tin protoporphyrin IX (SnPP), an HO-1 inhibitor, markedly abolished these beneficial effects of ALA in LPS-induced ALI. These results suggest that the protection mechanism of ALA may be through HO-1 induction and in turn suppressing NF-κB-mediated inflammatory responses.

6-Gingerol Ameliorates Sepsis Induced Acute Lung Injury by Regulating Nuclear Factor-κB and Nuclear-Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Signaling Pathways

2020 ◽  
Vol 19 (3) ◽  
pp. 255-260
Author(s):  
Fan Yang ◽  
Lu Deng ◽  
MuHu Chen ◽  
Ying Liu ◽  
Jianpeng Zheng
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Alveolar Collapse ◽  
Factor Α

Acute lung injury initiated systemic inflammation leads to sepsis. Septic mice show a series of degenerative changes in lungs as demonstrated by pulmonary congestion, alveolar collapse, inflammatory cell infiltration, and increased wet-todry weight in lungs. 6-Gingerol ameliorates histopathological changes and clinical outcome of the sepsis. The increase in the levels of tumor necrosis factor-α, interleukin-1 beta, interleukin-6, and interleukin-18 in septic mice were reduced by administration with 6-Gingerol. Also, 6-Gingerol attenuates sepsis-induced increase of malonaldehyde and decrease of catalase, superoxide, and glutathione. Enhanced phospho-p65, reduced nuclear factor erythropoietin-2-related factor 2, and heme oxygenase 1 in septic mice were reversed by administration with 6-Gingerol. In conclusion, 6-Gingerol demonstrates anti-inflammatory and antioxidant effects against sepsis associated acute lung injury through inactivation of nuclear factor-kappa B and activation of nuclear-factor erythroid 2-related factor 2 pathways.

Protective Effects of Heme Oxygenase-1 in Acute Lung Injury

CHEST Journal ◽  
1999 ◽  
Vol 116 ◽  
pp. 61S-63S ◽  
Author(s):  
Leo E. Otterbein ◽  
Patty J. Lee ◽  
Beek Yoke Chin ◽  
Irina Petrache ◽  
Sharon L. Camhi ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Protective Effects

scholarly journals Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 198 ◽  
Author(s):  
Ba-Wool Lee ◽  
Ji-Hye Ha ◽  
Han-Gyo Shin ◽  
Seong-Hun Jeong ◽  
Da-Bin Jeon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Herbal Remedy ◽  
Related Factor ◽  
Nuclear Factor ◽  
Tnf Α

Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.

Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury

2000 ◽  
Vol 279 (6) ◽  
pp. L1137-L1145 ◽  
Author(s):  
Edward Abraham ◽  
Aaron Carmody ◽  
Robert Shenkar ◽  
John Arcaroli
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Nuclear Factor Κb ◽  
Lung Edema ◽  
Protein Levels ◽  
Inflammatory Protein ◽  
Transcriptional Regulatory ◽  
Tnf Α ◽  
Factor Α

Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-κB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1β (IL-1β), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1β, MIP-2, and TNF-α were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1β and MIP-2 but not in TNF-α expression in the lungs after endotoxemia. These experiments show that neutrophils play a centrol role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.

scholarly journals αKlotho deficiency in acute kidney injury contributes to lung damage

2016 ◽  
Vol 120 (7) ◽  
pp. 723-732 ◽  
Author(s):  
Priya Ravikumar ◽  
Liping Li ◽  
Jianfeng Ye ◽  
Mingjun Shi ◽  
Masatomo Taniguchi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Oxidative Damage ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Lung Epithelial Cells ◽  
Lung Edema ◽  
Related Factor ◽  
Antioxidative Capacity

αKlotho is a circulating protein that originates predominantly from the kidney and exerts cytoprotective effects in distant sites. We previously showed in rodents that the lung is particularly vulnerable to αKlotho deficiency. Because acute lung injury is a common and serious complication of acute kidney injury (AKI), we hypothesized that αKlotho deficiency in AKI contributes to lung injury. To test the hypothesis, we created AKI by renal artery ischemia-reperfusion in rats and observed the development of alveolar interstitial edema and increased pulmonary oxidative damage to DNA, protein, and lipids. Administration of αKlotho-containing conditioned media 6 h post-AKI did not alter plasma creatinine but improved recovery of endogenous αKlotho production 3 days post-AKI, reduced lung edema and oxidative damage, and increased endogenous antioxidative capacity in the lung. Intravenously injected αKlotho rapidly exits alveolar capillaries as a macromolecule, suggesting transcytosis and direct access to the epithelium. To explore the epithelial action of αKlotho, we simulated oxidative stress in vitro by adding hydrogen peroxide to cultured A549 lung epithelial cells. Purified recombinant αKlotho directly protected cells at 20 pM with half-maximal effects at 40-50 pM, which is compatible with circulating αKlotho levels. Addition of recombinant αKlotho activated an antioxidant response element reporter and increased the levels of target proteins of the nuclear factor erythroid-derived 2 related factor system. In summary, αKlotho deficiency in AKI contributes to acute lung injury by reducing endogenous antioxidative capacity and increasing oxidative damage in the lung. αKlotho replacement partially reversed these abnormalities and mitigated pulmonary complications in AKI.

scholarly journals Quercetin Potentiates Docosahexaenoic Acid to Suppress Lipopolysaccharide-induced Oxidative/Inflammatory Responses, Alter Lipid Peroxidation Products, and Enhance the Adaptive Stress Pathways in BV-2 Microglial Cells

2019 ◽  
Vol 20 (4) ◽  
pp. 932 ◽  
Author(s):  
Grace Sun ◽  
Runting Li ◽  
Bo Yang ◽  
Kevin Fritsche ◽  
David Beversdorf ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Inflammatory Responses ◽  
Microglial Cells ◽  
Mammalian Brain ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Brain Functions ◽  
Study Results

High levels of docosahexaenoic acid (DHA) in the phospholipids of mammalian brain have generated increasing interest in the search for its role in regulating brain functions. Recent studies have provided evidence for enhanced protective effects when DHA is administered in combination with phytochemicals, such as quercetin. DHA and quercetin can individually suppress lipopolysaccharide (LPS)–induced oxidative/inflammatory responses and enhance the antioxidative stress pathway involving nuclear factor erythroid-2 related factor 2 (Nrf2). However, studies with BV-2 microglial cells indicated rather high concentrations of DHA (IC50 in the range of 60–80 µM) were needed to produce protective effects. To determine whether quercetin combined with DHA can lower the levels of DHA needed to produce protective effects in these cells is the goal for this study. Results showed that low concentrations of quercetin (2.5 µM), in combination with DHA (10 µM), could more effectively enhance the expression of Nrf2 and heme oxygenase 1 (HO-1), and suppress LPS–induced nitric oxide, tumor necrosis factor-α, phospho-cytosolic phospholipase A2, reactive oxygen species, and 4-hydroxynonenal, as compared to the same levels of DHA or quercetin alone. These results provide evidence for the beneficial effects of quercetin in combination with DHA, and further suggest their potential as nutraceuticals for improving health.

scholarly journals Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Wen Ye ◽  
Chenlei Zheng ◽  
Dinglai Yu ◽  
Fan Zhang ◽  
Reguang Pan ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Inflammatory Factor ◽  
Lipoxin A4 ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory

Acute lung injury (ALI) is a critical event involved in the pathophysiological process of acute pancreatitis (AP). Many methods have been widely used for the treatment of AP-ALI, but few are useful during early inflammation. Lipoxin A4 (LXA4), a potent available anti-inflammatory and novel antioxidant mediator, has been extensively studied in AP-ALI, but its underlying mechanism as a protective mediator is not clear. This research was conducted to identify the possible targets and mechanisms involved in the anti-AP-ALI effect of LXA4. First, we confirmed that LXA4 strongly inhibited AP-ALI in mice. Next, using ELISA, PCR, and fluorescence detection to evaluate different parameters, LXA4 was shown to reduce the inflammatory cytokine production induced by AP and block reactive oxygen species (ROS) generation in vivo and in vitro. In addition, TNF-α treatment activated the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream gene heme oxygenase-1 (HO-1) in human pulmonary microvascular endothelial cells (HPMECs), and LXA4 further promoted their expression. This study also provided evidence that LXA4 phosphorylates Ser40 and triggers its nuclear translocation to activate Nrf2. Moreover, when Nrf2-knockout (Nrf2-/-) mice and cells were used to further assess the effect of the Nrf2/HO-1 pathway, we found that Nrf2 expression knockdown partially eliminated the effect of LXA4 on the reductions in inflammatory factor levels while abrogating the inhibitory effect of LXA4 on the ROS generation stimulated by AP-ALI. Overall, LXA4 attenuated the resolution of AP-induced inflammation and ROS generation to mitigate ALI, perhaps by modulating the Nrf2/HO-1 pathway. These findings have laid a foundation for the treatment of AP-ALI.

Sign in / Sign up

Export Citation Format

Share Document