Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model

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.

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Shen-su-yin, a Traditional Herbal Medicine, Attenuates Lipopolysaccharide-induced Acute Lung Injury in Rats Through Its Anti-inflammatory and Anti-oxidative Effects

10.21203/rs.3.rs-1089681/v1 ◽

2021 ◽

Author(s):

Peng Xiao ◽

Jun Ke ◽

Jiuyun Zhang ◽

Haijun Zhou ◽

Wuhong Zheng

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Weight Ratio ◽

Oxygenation Index ◽

Dry Weight ◽

Signalling Pathway ◽

Lung Injury Score ◽

High Dose ◽

Histopathological Analysis ◽

Anti Inflammatory

Abstract Most components of Shen-su-yin (SSY), an herbal formula, have anti-inflammatory and antioxidant activities. The present study was designed to investigate potential effects and mechanisms of SSY on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. 48 rats were randomly divided into 4 groups: control (Ctrl) group, LPS-induced ALI group, low- (SSY-LD) and high- (SSY-HD) dose SSY-treated ALI group. SSY was administered to SSY-treated rats immediately after LPS induction. After 24 hours, blood gas analysis and lactate determination were performed; and bronchoalveolar lavage fluid was collected for detecting protein concentration and levels of cytokines. Lung tissues were obtained for Western blot analysis, histopathological analysis, wet-to-dry weight ratio calculation and measurement of oxidative stress levels. SSY improved oxygenation index and mean arterial pressure, decreased levels of lactate and heart rate, alleviated lung histopathology indexes including lung injury score, wet-to-dry weight ratio and exudation of protein as well as inflammatory cells in ALI rats. Furthermore, SSY reduced levels of pro-inflammatory and oxidative mediums, while increasing levels of anti-inflammatory cytokine and anti-oxidative activity in lung tissues. SSY also suppressed NF-κB signalling pathway and further activated Keap1-Nrf2-ARE signalling pathway activated by LPS. Moreover, all the effects caused by SSY in the SSY-HD group were more encouraging than those in the SSY-LD group. The results indicate that the preventive use of SSY can alleviate ALI through the anti-inflammatory and antioxidant effects mediated by inhibition of NF-κB signalling pathway and activation of Keap1-Nrf2-ARE signalling pathway, and the effect of high dose is better.

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Shikonin exerts anti-inflammatory effects in a murine model of lipopolysaccharide-induced acute lung injury by inhibiting the nuclear factor-kappaB signaling pathway

International Immunopharmacology ◽

10.1016/j.intimp.2013.04.020 ◽

2013 ◽

Vol 16 (4) ◽

pp. 475-480 ◽

Cited By ~ 43

Author(s):

Dejie Liang ◽

Yong Sun ◽

Yongbin Shen ◽

Fengyang Li ◽

Xiaojing Song ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

Murine Model ◽

Nuclear Factor Kappab ◽

Nuclear Factor ◽

Anti Inflammatory

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Sinoacutine inhibits inflammatory responses to attenuates acute lung injury by regulating NF-κB and JNK signaling pathways

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03458-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuancui Zhao ◽

Lili Cui ◽

Xing Xin Yang ◽

Xingqian Sun ◽

Yunkuan Liu ◽

...

Keyword(s):

Gene Expression ◽

Nitric Oxide ◽

Acute Lung Injury ◽

Lung Injury ◽

Western Blot ◽

Blot Analysis ◽

Western Blot Analysis ◽

Signalling Pathway ◽

Tnf Α ◽

Anti Inflammatory

Abstract Background Stephania yunnanensis H. S. Lo is widely used as an antipyretic, analgesic and anti-inflammatory herbal medicine in SouthWest China. In this study, we investigated the anti-inflammatory activity and mechanism of sinoacutine (sino), one of the primary components extracted from this plant. Methods A RAW264.7 cell model was established using lipopolysaccharide (LPS) induced for estimation of cytokines in vitro, qPCR was used to estimate gene expression, western blot analysis was used to estimate protein level and investigate the regulation of NF- κB, JNK and MAPK signal pathway. In addition, an acute lung injury model was established to determine lung index and levels of influencing factors. Results Using the RAW264.7 model, we found that sino reduced levels of nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and prostaglandin E2 (PGE2) but increased levels of IL-6. qPCR analysis revealed that sino (50, 25 μg/ml) inhibited gene expression of nitric oxide synthase (iNOS). western blot analysis showed that sino significantly inhibited protein levels of both iNOS and COX-2. Further signalling pathway analysis validated that sino also inhibited phosphorylation of p65 in the NF-κB and c-Jun NH2 terminal kinase (JNK) signalling pathways but promoted the phosphorylation of extracellular signal regulated kinase (ERK) and p38 in the MAPK signalling pathway. In addition, in a mouse model induced by LPS, we determined that sino reduced the lung index and the levels of myeloperoxidase (MPO), NO, IL-6 and TNF-α in lung tissues and bronchoalveolar lavage fluid (BALF) in acute lung injury (ALI). Conclusion Taken together, our results demonstrate that sino is a promising drug to alleviate LPS-induced inflammatory reactions.

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Sitagliptin activates the p62–Keap1–Nrf2 signalling pathway to alleviate oxidative stress and excessive autophagy in severe acute pancreatitis-related acute lung injury

Cell Death and Disease ◽

10.1038/s41419-021-04227-0 ◽

2021 ◽

Vol 12 (10) ◽

Author(s):

Lingming Kong ◽

Jie Deng ◽

Xiang Zhou ◽

Binbin Cai ◽

Baofu Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Pancreatitis ◽

Acute Lung Injury ◽

Lung Injury ◽

Severe Acute Pancreatitis ◽

Nuclear Translocation ◽

Signalling Pathway ◽

Ros Production ◽

Nrf2 Knockout ◽

Anti Inflammatory

AbstractAcute lung injury (ALI) is a complication of severe acute pancreatitis (SAP). Sitagliptin (SIT) is a DPP4 inhibitor that exerts anti-inflammatory and antioxidant effects; however, its mechanism of action in SAP-ALI remains unclear. In this study, we investigated the effects of SIT on SAP-ALI and the specific pathways involved in SAP-induced lung inflammation, including oxidative stress, autophagy, and p62–Kelch-like ECH-associated protein 1 (Keap1)–NF-E2-related factor 2 (Nrf2) signalling pathways. Nrf2 knockout (Nrf2−/−) and wild-type (WT) mice were pre-treated with SIT (100 mg/kg), followed by caerulein and lipopolysaccharide (LPS) administration to induce pancreatic and lung injury. BEAS-2B cells were transfected with siRNA-Nrf2 and treated with LPS, and the changes in inflammation, reactive oxygen species (ROS) levels, and autophagy were measured. SIT reduced histological damage, oedema, and myeloperoxidase activity in the lung, decreased the expression of pro-inflammatory cytokines, and inhibited excessive autophagy and ROS production via the activation of the p62–Keap1–Nrf2 signalling pathway and promotion of the nuclear translocation of Nrf2. In Nrf2-knockout mice, the anti-inflammatory effect of SIT was reduced, resulting in ROS accumulation and excessive autophagy. In BEAS-2B cells, LPS induced ROS production and activated autophagy, further enhanced by Nrf2 knockdown. This study demonstrates that SIT reduces SAP-ALI-associated oxidative stress and excessive autophagy through the p62–Keap1–Nrf2 signalling pathway and nuclear translocation of Nrf2, suggesting its therapeutic potential in SAP-ALI.

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