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

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.

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LncRNA HOTAIR Increases Inflammatory Responses by Activating NF-κB Pathway in LPS-Induced Acute Lung Injury

10.21203/rs.3.rs-49969/v1 ◽

2020 ◽

Author(s):

XiaoMei Huang ◽

ZeXun Mo ◽

YuJun Li ◽

Hua He ◽

KangWei Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Noncoding Rna ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

A549 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Qrt Pcr ◽

Tnf Α ◽

Lncrna Hotair

Abstract Background Nuclear factor kappa-B (NF-κB) activation increased the expression of cytokines and further lead to lung injury was considered the main mechanism of acute lung injury (ALI). Here, we focus on exploring the potential regulatory mechanism between long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) and NF-κB on LPS-induced ALI. Methods A549 cells were then divided into 4 groups: HOTAIR group, NC group, si-HOTAIR group and si-NC group. These 4 groups were then treated with 1μg/mL lipopolysaccharides (LPS) or without LPS at 37°C for 24 h. The expression level of cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) and LncRNA HOTAIR were evaluated by quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). Western Blot analysis was adopted for evaluating the level of p-IκBα/IκBα and p-p65/p65. Nuclear translocation of p65 was observed by immunofluorescence staining. Results qRT-PCR and ELISA assay showed that the expression of cytokines (IL-1β, IL-6 and TNF-α) and inflammatory gene HOTAIR was remarkably increased with LPS treatment (p < 0.01). Over-expression of HOTAIR significantly increased the expression of cytokines (including IL-1β, IL-6 and TNF-α) and NF-κB pathway associated proteins (including p-IκBα/IκBα and p-p65/p65), while knockdown of HOTAIR had the opposite effect (p < 0.01). The immunofluorescence assay showed that the level of p65 in the nucleus was significantly higher in the HOTAIR group and significantly lowers in the si-HOTAIR group (p < 0.01). Conclusion HOTAIR may play a pro-inflammatory response through NF-κB pathway in LPS-induced ALI, which may provide a perspective for further understanding the pathogenic mechanism of ALI.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/590363 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 22

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.

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Seabuckthorn Paste Protects Lipopolysaccharide-Induced Acute Lung Injury in Mice through Attenuation of Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4130967 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Leilei Du ◽

Xiaoxin Hu ◽

Chu Chen ◽

Tingting Kuang ◽

Hengfu Yin ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Nuclear Translocation ◽

Body Weight Loss ◽

Tibetan Medicine ◽

Related Factor ◽

Dependent Manner ◽

Protective Effects ◽

Lps Challenge

Oxidative stress is one of the major mechanisms implicated in endotoxin-induced acute lung injury. Seabuckthorn paste (SP), a traditional Tibetan medicine with high content of polyphenols and remarkable antioxidant activity, is commonly used in treating pulmonary diseases. In the present study, the protective effects and possible underlying mechanisms of SP on lipopolysaccharide- (LPS-) induced acute lung injury in mice were investigated. It was found that body weight loss, lung tissue microstructure lesions, transvascular leakage increase, malondialdehyde augmentation, and the reduction of superoxide dismutase and glutathione peroxidase levels caused by LPS challenge were all consistently relieved by SP treatment in a dose-dependent manner. Moreover, accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in lung nuclei caused by SP treatment was observed. Our study demonstrated that SP can provide significant protection against LPS-induced acute lung injury through maintaining redox homeostasis, and its mechanism involves Nrf2 nuclear translocation and activation.

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Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes

Molecules ◽

10.3390/molecules26113174 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3174

Author(s):

Nhung Quynh Do ◽

Shengdao Zheng ◽

Bom Park ◽

Quynh T. N. Nguyen ◽

Bo-Ram Choi ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathways ◽

High Glucose ◽

Skin Diseases ◽

Inflammatory Responses ◽

Human Keratinocytes ◽

Related Factor ◽

Nuclear Factor ◽

Fruit Extract ◽

Activated T Cells

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

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(–)-Loliolide Isolated from Sargassum horneri Suppressed Oxidative Stress and Inflammation by Activating Nrf2/HO-1 Signaling in IFN-γ/TNF-α-Stimulated HaCaT Keratinocytes

Antioxidants ◽

10.3390/antiox10060856 ◽

2021 ◽

Vol 10 (6) ◽

pp. 856

Author(s):

Eui-Jeong Han ◽

Ilekuttige Priyan Shanura Fernando ◽

Hyun-Soo Kim ◽

Dae-Sung Lee ◽

Areum Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Nuclear Factor Κb ◽

Sargassum Horneri ◽

Mitogen Activated Protein Kinase ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Hacat Keratinocytes ◽

Tnf Α ◽

Ifn Γ

The present study evaluated the effects of (–)-loliolide isolated from Sargassum horneri (S. horneri) against oxidative stress and inflammation, and its biological mechanism in interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocytes. The results showed that (–)-loliolide improved the cell viability by reducing the production of intracellular reactive oxygen species (ROS) in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. In addition, (–)-loliolide effectively decreased the expression of inflammatory cytokines (interleukin (IL)-4 IL-6, IL-13, IFN-γ and TNF-α) and chemokines (CCL11 (Eotaxin), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)), by downregulating the expression of epidermal-derived initial cytokines (IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)). Furthermore, (–)-loliolide suppressed the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling, whereas it activated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Interestingly, the cytoprotective effects of (–)-loliolide against IFN-γ/TNF-α stimulation were significantly blocked upon inhibition of HO-1. Taken together, these results suggest that (–)-loliolide effectively suppressed the oxidative stress and inflammation by activating the Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes.

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The nanocomposite fullerol reduces oxidative stress, pulmonary injury, and mortality in a rat model of acute lung injury

10.22541/au.163252259.97677391/v1 ◽

2021 ◽

Author(s):

Rosária Aires ◽

Ildernandes Vieira-Alves ◽

Leda Maria Coimbra-Campos ◽

Marina Ladeira ◽

Teresa Socarras ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

High Mortality ◽

Therapeutic Potential ◽

Ex Vivo ◽

Mortality Rates ◽

Kaplan Meier ◽

Pulmonary Damage

BACKGROUND AND PURPOSE Acute lung injury (ALI) is a critical disorder that has high mortality rates, and pharmacological therapies are so far ineffective. The pathophysiology of ALI involves pulmonary oxidative stress and inflammatory response. Fullerol is a carbon nanocomposite that possesses antioxidant and anti-inflammatory properties. Here, we evaluated the therapeutic potential of fullerol and its mechanisms in a model of paraquat-induced ALI. EXPERIMENTAL APPROACH Rats were divided into ALI (paraquat alone), fullerol (paraquat plus fullerol), and control groups. Survival curves were estimated using the Kaplan-Meier method. The myeloperoxidase assay, ELISA, and hematoxylin and eosin staining were used to determine neutrophils infiltration, cytokines production, and histopathological parameters in lung samples, respectively. The antioxidant effect of fullerol was evaluated in vitro and ex vivo. KEY RESULTS Fullerol (0.01 to 0.3 mg/kg) markedly reduced the severe lung injury and high mortality rates observed in ALI rats. Moreover, fullerol (0.03 mg/kg) inhibited the reactive oxygen species formation and lipid peroxidation seen in lungs from ALI rats, and exhibited a potent concentration-dependent (10 to 10 mg/ml) in vitro antioxidant activity. Importantly, fullerol (0.03 mg/kg) inhibited neutrophils accumulation in bronchoalveolar lavage and lungs, and the increase in pulmonary levels of TNF-α, IL-1β, IL-6, and CINC-1 in ALI rats. CONCLUSIONS AND IMPLICATIONS Fullerol treatment was effective in reducing pulmonary damage and ALI-induced mortality, highlighting its therapeutic potential in an ALI condition. Searching for new pharmacological therapies to treat ALI may be desirable especially in view of the new coronavirus disease 2019 that currently plagues the world.

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Huangkui Capsule Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Macrophage Activation by Suppressing Inflammation and Oxidative Stress in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6626483 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Jinfang Deng ◽

Zhenpeng He ◽

Xiuru Li ◽

Wei Chen ◽

Ziwen Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Macrophage Activation ◽

Neutrophil Infiltration ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Myeloperoxidase Activity ◽

Tnf Α ◽

And Oxidative Stress

Background. Huangkui capsule (HKC) comprises the total flavonoid extract of flowers of Abelmoschus manihot (L.) Medicus. This study aimed to explore the effects of HKC on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells. Methods. Enzyme-linked immunosorbent assay, histopathology, spectrophotometry, and quantitative real-time polymerase chain reaction were used for the assessments. Statistical analysis was performed using a one-way analysis of variance. Results. LPS significantly increased lung inflammation, neutrophil infiltration, and oxidative stress and downregulated lung miR-451 expression. Treatment with HKC dramatically attenuated the lung wet/dry weight ratio, reduced the total cell count in the bronchoalveolar lavage fluid (BALF), and inhibited myeloperoxidase activity in the lung tissues 24 h after LPS challenge. Histopathological analysis demonstrated that HKC attenuated LPS-induced tissue oedema and neutrophil infiltration in the lung tissues. Additionally, the concentrations of tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 in BALF and IL-6 in the plasma reduced after HKC administration. Moreover, HKC could enhance glutathione peroxidase and catalase activities and upregulate the expression of miR-451 in the lung tissues. In vitro experiments revealed that HKC inhibited the production of nitric oxide, TNF-α, and IL-6 in LPS-induced RAW 264.7 cells and mouse primary peritoneal macrophages. Additionally, HKC downregulated LPS-induced transcription of TNF-α and IL-6 in RAW 264.7 cells. Conclusions. These findings suggest that HKC has anti-inflammatory and antioxidative effects that may protect mice against LPS-induced ALI and macrophage activation.

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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

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:255-260 ◽

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.

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(10Z)-Debromohymenialdisine from Marine Sponge Stylissa sp. Regulates Intestinal Inflammatory Responses in Co-Culture Model of Epithelial Caco-2 Cells and THP-1 Macrophage Cells

Molecules ◽

10.3390/molecules24183394 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3394 ◽

Cited By ~ 2

Author(s):

Seon Min Lee ◽

Na-Hyun Kim ◽

Sangbum Lee ◽

Yun Na Kim ◽

Jeong-Doo Heo ◽

...

Keyword(s):

Marine Sponge ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Subsequent Increase ◽

Vitro Model ◽

Factor Α

Crohn’s disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10Z)-debromohymenialdisine (1) isolated from marine sponge Stylissa species using an intestinal in vitro model with a transwell co-culture system. The treatment with 1 attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1β, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1–5 μM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that 1 markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of 1 as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.

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The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00449.2016 ◽

2017 ◽

Vol 312 (2) ◽

pp. L155-L162 ◽

Cited By ~ 49

Author(s):

Hailin Zhao ◽

Shiori Eguchi ◽

Azeem Alam ◽

Daqing Ma

Keyword(s):

Lung Injury ◽

Therapeutic Potential ◽

Antioxidant Response ◽

Protective Role ◽

Chronic Obstructive ◽

Related Factor ◽

Nuclear Factor ◽

Obstructive Pulmonary Disease ◽

Antioxidant Response Elements

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents, and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an ARE. Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury, abnormal inflammatory and immune responses, and apoptosis. The Nrf2-antioxidant pathway has been shown to be important in the protection against various lung injuries including acute lung injury/acute respiratory distress syndrome and bronchopulmonary dysplasia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and allergy and was widely examined for new therapeutic targets. The present review explores the protective role of Nrf-2 against lung injury and the therapeutic potential in targeting Nrf-2.

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