Juglone Attenuates Sepsis-Induced Acute Lung Injury via Suppression of the TLR4/Nf-κb Pathway

2020 ◽  
Vol 18 (2) ◽  
pp. 201-206
Author(s):  
Qiu Nan ◽  
Xu Xinmei ◽  
He Yingying ◽  
Fan Chengfen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Cecal Ligation ◽  
Myeloperoxidase Activity ◽  
Nuclear Factor ◽  
Cecal Ligation And Puncture ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa

Sepsis, with high mortality, induces deleterious organ dysfunction and acute lung injury. Natural compounds show protective effect against sepsis-induced acute lung injury. Juglone, a natural naphthoquinone, demonstrates pharmacological actions as a pro-apoptotic substrate in tumor treatment and anti-inflammation substrate in organ injury. In this study, the influence of juglone on sepsis-induced acute lung injury was investigated. First, a septic mice model was established via cecal ligation and puncture, and then verified via histopathological analysis of lung tissues, the wet/dry mass ratio and myeloperoxidase activity was determined. Cecal ligation and puncture could induce acute lung injury in septic mice, as demonstrated by alveolar damage and increase of wet/dry mass ratio and myeloperoxidase activity. However, intragastric administration juglone attenuated cecal ligation and puncture-induced acute lung injury. Secondly, cecal ligation and puncture-induced increase of inflammatory cells in bronchoalveolar lavage fluid was also alleviated by the administration of juglone. Similarly, the protective effect of juglone against cecal ligation and puncture-induced acute lung injury was accompanied by a reduction of pro-inflammatory factor secretion in bronchoalveolar lavage fluid and lung tissues. Cecal ligation and puncture could activate toll-like receptor 4/nuclear factor-kappa B signaling pathway, and administration of juglone suppressed toll-like receptor 4/nuclear factor-kappa B activation. In conclusion, juglone attenuated cecal ligation and puncture-induced lung damage and inflammatory response through inactivation of toll-like receptor 4/nuclear factor-kappa B, suggesting a potential therapeutic strategy in the treatment of sepsis-induced acute lung injury.

Bilobalide Ameliorates Sepsis Induced Acute Lung Injury by Inactivating Toll-Like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-Kappa B Pathway

2020 ◽  
Vol 19 (3) ◽  
pp. 277-282
Author(s):  
Tian Liu ◽  
Siyi Jiang ◽  
Shengwei Jia ◽  
Fuxiang Fan
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Cecal Ligation ◽  
Myeloid Differentiation ◽  
Nuclear Factor ◽  
Cecal Ligation And Puncture ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Myeloid Differentiation Factor

Acute lung injury refers to the injury of alveolar epithelial cells and pulmonary capillary endothelial cells caused by noncardiac factors. To better combat the disease, there is an urgent need to develop more effective drugs. Sepsis is a syndrome of systemic inflammation caused by infection, and the molecular mechanism by which sepsis induces acute lung injury has not been clearly determined. Bilobalide is a unique component of Ginkgo biloba. Although it has multiple biological functions, its role in sepsis induced acute lung injury needs further study. In this study, we found that bilobalide alleviated cecal ligation and puncture induced acute lung injury. Additionally, bilobalide regulated cecal ligation and puncture induced lung injury through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway. We therefore conclude that bilobalide may be a potential drug for the treatment of sepsis induced acute lung injury.

Chelidonine Attenuates Sepsis-Induced Acute Lung Injury via Suppressing Toll-like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-॔B Signaling Pathway in Newborn Mice

2020 ◽  
Vol 19 (1) ◽  
pp. 120-126
Author(s):  
Ayinuerguli Adili ◽  
Adilijiang Kari ◽  
Chuanlong Song ◽  
Abulaiti Abuduhaer
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Myeloid Differentiation ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Inflammatory Infiltration ◽  
Newborn Mice ◽  
Myeloid Differentiation Factor

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.

Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

2019 ◽  
Vol 18 (2) ◽  
pp. 176-182
Author(s):  
Chen Weiyan ◽  
Deng Wujian ◽  
Chen Songwei
Keyword(s):  
Acute Lung Injury ◽  
B Cells ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Light Chain ◽  
Cecal Ligation ◽  
Nuclear Factor ◽  
Kappa Light Chain ◽  
Cecal Ligation And Puncture ◽  
Light Chain Enhancer

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

scholarly journals A Standardized Traditional Chinese Medicine Preparation Named Yejuhua Capsule Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Downregulating Toll-Like Receptor 4/Nuclear Factor-κB

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Chu-Wen Li ◽  
Zhi-Wei Chen ◽  
Xiao-Li Wu ◽  
Zhao-Xiao Ning ◽  
Zu-Qing Su ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Lung Injury ◽  
Therapeutic Drug ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Traditional Chinese Medicine Preparation

A standardized traditional Chinese medicine preparation named Yejuhua capsule (YJH) has been clinically used in treatments of various acute respiratory system diseases with high efficacy and low toxicity. In this study, we were aiming to evaluate potential effects and to elucidate underlying mechanisms of YJH against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. Moreover, the chemical analysis and chromatographic fingerprint study were performed for quality evaluation and control of this drug. ALI was induced by intratracheal instillation of LPS (5 mg/kg) into the lung in mice and dexamethasone (5 mg/kg, p.o.) was used as a positive control drug. Results demonstrated that pretreatments with YJH (85, 170, and 340 mg/kg, p.o.) effectively abated LPS-induced histopathologic changes, attenuated the vascular permeability enhancement and edema, inhibited inflammatory cells migrations and protein leakages, suppressed the ability of myeloperoxidase, declined proinflammatory cytokines productions, and downregulated activations of nuclear factor-κB (NF-κB) and expressions of toll-like receptor 4 (TLR4). This study demonstrated that YJH exerted potential protective effects against LPS-induced ALI in mice and supported that YJH was a potential therapeutic drug for ALI in clinic. And its mechanisms were at least partially associated with downregulations of TLR4/NF-κB pathways.

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