scholarly journals Examination of the protective effect of 6-shogaol against LPS-induced acute lung injury in mice via NF-kB attenuation

2016 ◽  
Vol 68 (3) ◽  
pp. 633-639 ◽  
Author(s):  
Jing-Chao Wang ◽  
Li-Hua Zhou ◽  
Hai-Jin Zhao ◽  
Shao-Xi Cai
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Histopathological Examination ◽  
Pathological Condition ◽  
Causative Factor ◽  
Docking Study ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Factor Alpha

Acute lung injury (ALI), the causative factor for acute respiratory distress syndrome, results in significant morbidity and mortality. Due to a lack of effective therapeutic options for ALI, the development of novel therapies is urgently needed. NF-?B, an inflammatory mediator necessary for the evolution of ALI, could serve as an important target for novel agents to prevent disease progression. The present study was designed to evaluate the protective effect of 6-shogaol against lipopolysaccharide (LPS)-induced ALI in mice, and its mechanism of action. Our results suggest that 6-shogaol significantly attenuates elevated levels of various proinflammatory cytokines, such as tumor necrosis factor alpha (TNF?), IL-1? and IL-6. Moreover, the influx of neutrophils, increased protein concentration and edema were also suppressed in mice pretreated with 6-shogaol. These observations were also confirmed by histopathological examination of lung tissues, which suggests that 6-shogaol significantly improves the pathological condition to normal in a dose-dependent manner. A docking study of 6-shogaol was also performed, with the NF-?B p50 homodimer bound to a ?B site, to determine its possible inhibitory effects. Our results show that 6-shogaol was efficiently accommodated in the deep cleft of the active site, lined with residues Tyr57, Val58 and Cys59, Tyr143, Lys145 and Lys146 of Chain B of p50 NF-?B.

scholarly journals Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Shuiqiao Fu ◽  
Weina Lu ◽  
Wenqiao Yu ◽  
Jun Hu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Weight Ratio ◽  
Cordyceps Sinensis ◽  
Myeloperoxidase Activity ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tnf Α ◽  
Cox 2

Abstract Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice. Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1β, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05). Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.

Protective effect of mepacrine on hypoxia-reoxygenation-induced acute lung injury in rats

1995 ◽  
Vol 78 (1) ◽  
pp. 225-231 ◽  
Author(s):  
C. Y. Shen ◽  
D. Wang ◽  
M. L. Chang ◽  
K. Hsu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tnf Alpha ◽  
Lung Weight ◽  
Necrosis Factor Alpha ◽  
Alpha Production ◽  
Hypoxia Reoxygenation

Mepacrine, a cell membrane stabilizer and inhibitor of phospholipase A2 (PLA2), exerts a protective effect on ischemia-reperfusion injury in heart; however, its effect in lungs has not been examined. This study aimed to determine whether mepacrine pretreatment attenuates ischemia-reperfusion lung injury simulated by hypoxia reoxygenation and to identify possible mechanisms for such protection. Acute lung injury was induced in Sprague-Dawley rats by ventilation with 5% CO2–95% N2 and 5% CO2–95% air. Pretreatment with 0.06 mM mepacrine significantly attenuated the acute lung injury. Capillary filtration coefficient, lung weight gain, and protein concentration of lung lavage fluid were significantly lower in mepacrine-treated rats than in rats exposed to hypoxia reoxygenation alone. Steroid dexamethasone, another potential PLA2 inhibitor, had almost no protective effect. Mepacrine but not dexamethasone caused dose-dependent attenuation of the increase in leukocyte chemiluminescence produced by exposure to phorbol myristate acetate. Mepacrine also dose-dependently inhibited production of tumor necrosis factor-alpha (TNF-alpha) by human monocytes; dexamethasone was much less effective in decreasing TNF-alpha production. We conclude that mepacrine but not dexamethasone can significantly attenuate a hypoxia-reoxygenation-induced injury of the lung. This protective effect of mepacrine may not be the result of its inhibition of PLA2 but rather of its downregulation of oxygen radical production by circulating or resident leukocytes or its attenuation of TNF-alpha production by macrophages.

scholarly journals Protective Effect of Corynoline in Sepsis-Induced Acute Lung Injury in Rats via Inhibition of NF-ĸB

2020 ◽  
Vol 15 (11) ◽  
pp. 1934578X2096118
Author(s):  
Min Shu ◽  
Yulu Tang ◽  
Jianzhen Liu
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Lung Tissue ◽  
Significant Inhibition ◽  
Tissue Homogenate ◽  
Necrosis Factor Alpha ◽  
Lung Tissue Homogenate ◽  
And Migration

The present study was conducted to determine the effect of corynoline (COR) against sepsis-induced acute lung injury (ALI) in Wistar rats. Results of the study suggested that COR causes significant inhibition of lipid peroxidation (malondialdehyde) together with inhibition of oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and myeloperoxidase). The level of various proinflammatory (tumor necrosis factor-alpha, interleukin-8, and migration inhibitory factor) was also found to be reduced in COR-treated rats after sepsis. The protective effect of COR was further substantiated by the histopathology of lung tissue, where it improves the architecture of alveolar spaces. In western blot analysis, COR causes significant inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells activation in the lung tissue homogenate. Our results demonstrated that COR was able to prevent the progression of ALI in rats via inhibition of inflammation and oxidative stress.

Bactericidal/permeability-increasing protein ameliorates acute lung injury in porcine endotoxemia

1994 ◽  
Vol 76 (5) ◽  
pp. 2006-2014 ◽  
Author(s):  
T. J. Vandermeer ◽  
M. J. Menconi ◽  
B. P. O′Sullivan ◽  
V. A. Larkin ◽  
H. Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Human Neutrophils ◽  
Cationic Protein ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
To Receive ◽  
Necrosis Factor

Bactericidal/permeability-increasing protein (BPI), a cationic protein isolated from human neutrophils, binds lipopolysaccharide (LPS), kills gram-negative bacteria, and neutralizes many of the effects of LPS in vitro and in vivo. We hypothesized that a recombinant 23-kDa NH2-terminal fragment of BPI (BPI23) would reduce acute lung injury in endotoxemic pigs. At -18 h, pigs received an intravenous priming dose of LPS (20 micrograms/kg). Anesthetized ventilated swine were randomized to receive 1) no further treatment (n = 4); 2) LPS (250 micrograms/kg over 50 min) and BPI23 (3-mg/kg bolus and 3 mg/kg over 60 min) (n = 6); or 3) LPS and thaumatin, a cationic protein devoid of LPS neutralizing activity that has a molecular mass and isoelectric point that are similar to that of BPI23 (n = 7). BPI23 treatment significantly ameliorated LPS-induced hypoxemia, functional upregulation of opsonin receptors on circulating phagocytes, and alveolitis but had no effect on the elaboration of tumor necrosis factor-alpha or thromboxane A2. The salutory effects of BPI23 on acute lung injury in endotoxemic pigs may be mediated, at least in part, by inhibition of direct activation of phagocytes by LPS.

scholarly journals Euphorbia cuneata Represses LPS-Induced Acute Lung Injury in Mice via Its Antioxidative and Anti-Inflammatory Activities

Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1620
Author(s):  
Hossam M. Abdallah ◽  
Dina S. El-Agamy ◽  
Sabrin R. M. Ibrahim ◽  
Gamal A. Mohamed ◽  
Wael M. Elsaed ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Lung Tissue ◽  
Histopathological Examination ◽  
Total Protein Content ◽  
Lps Challenge ◽  
Cell Counts ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Euphorbia cuneata (EC; Euphorbiaceae), which widely grows in Saudi Arabia and Yemen, is used traditionally to treat pain and inflammation. This study aimed to evaluate the protective anti-inflammatory effect of a standardized extract of EC against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible underlying mechanism(s) of this pharmacologic activity. ALI was induced in male Balb/c mice using intraperitoneal injection of LPS. A standardized total methanol extract of EC or dexamethasone was administered 5 days prior to LPS challenge. Bronchoalveolar fluid (BALF) and lung samples were collected for analysis. The results demonstrated the protective anti-inflammatory effect of EC against LPS-induced ALI in mice. Standardized EC contained 2R-naringenin-7-O-β-glucoside (1), kaempferol-7-O-β-glucoside (2), cuneatannin (3), quercetin (4), and 2R-naringenin (5) in concentrations of 6.16, 4.80, 51.05, 13.20, and 50.00 mg/g of extract, respectively. EC showed a protective effect against LPS-induced pulmonary damage. EC reduced lung wet/dry weight (W/D) ratio and total protein content in BALF, indicating attenuation of the pulmonary edema. Total and differential cell counts were decreased in EC-treated animals. Histopathological examination confirmed the protective effect of EC, as indicated by an amelioration of LPS-induced lesions in lung tissue. EC also showed a potent anti-oxidative property as it decreased lipid peroxidation and increased the antioxidants in lung tissue. Finally, the anti-inflammatory activity of EC was obvious through its ability to suppress the activation of nuclear factor-κB (NF-κB), and hence its reduction of the levels of downstream inflammatory mediators. In conclusion, these results demonstrate the protective effects of EC against LPS-induced lung injury in mice, which may be due to its antioxidative and anti-inflammatory activities.

scholarly journals In vitro and in vivo assessment of the protective effect of sufentanil in acute lung injury

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098635
Author(s):  
Qi Gao ◽  
Ningqing Chang ◽  
Donglian Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
High Mobility ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Hmgb1 Protein

Objectives To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI). Material and Methods Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI in vivo and in vitro. In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both in vivo and in vitro. Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed in vivo and in vitro following sufentanil treatment. miR-129-5p targeted the 3ʹ untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells. Conclusion Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.

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