Anti-inflammatory effects of curcumin in acute lung injury: In vivo and in vitro experimental model studies

Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.

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Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

Scientific Reports ◽

10.1038/s41598-021-01624-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Seongchan Kim ◽

Shin Young Kim ◽

Seung Joon Rho ◽

Seung Hoon Kim ◽

So Hyang Song ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Intratracheal Instillation ◽

Sprague Dawley ◽

In Vivo Experiments ◽

Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

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Hordenine Protects Against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Inflammation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.712232 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiyue Zhang ◽

Li Du ◽

Jinrong Zhang ◽

Chunyan Li ◽

Jie Zhang ◽

...

Keyword(s):

Acute Lung Injury ◽

Protein Kinase ◽

Lung Injury ◽

Biological Activities ◽

Mitogen Activated Protein Kinase ◽

Inflammatory Factors ◽

Enzyme Linked Immunosorbent Assay ◽

Anti Inflammatory

Acute lung injury (ALI) is a respiratory disease that leads to death in severe cases. Hordenine (Hor), a barley-derived natural product, has various biological activities, including anti-inflammatory, and anti-oxidation activities. We investigated the effect of Hor on lipopolysaccharide-induced ALI and its potential mechanism. The anti-inflammatory effects of Hor were detected using in vivo and in vitro models by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blotting, and molecular docking simulations. Hor inhibited increases in the levels of inflammatory factors both in vivo and in vitro, and its anti-inflammatory effect inhibited activation of protein kinase B, nuclear factor-κB, and mitogen-activated protein kinase signaling. Hor alleviated lipopolysaccharide-induced ALI by inhibiting inflammatory cytokine increases in vivo and in vitro and shows potential for preventing inflammatory disease.

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Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1

Molecules ◽

10.3390/molecules26196073 ◽

2021 ◽

Vol 26 (19) ◽

pp. 6073

Author(s):

Laily Rahmawati ◽

Nur Aziz ◽

Jieun Oh ◽

Yo Han Hong ◽

Byoung Young Woo ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Models ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Raw264.7 Cells ◽

Acute Gastritis ◽

Anti Inflammatory

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.

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The therapeutic effect of Bletilla striata extracts on LPS-induced acute lung injury by regulation of inflammation and oxidation

RSC Advances ◽

10.1039/c6ra17059e ◽

2016 ◽

Vol 6 (92) ◽

pp. 89338-89346 ◽

Cited By ~ 2

Author(s):

Yongjie Wang ◽

Weizhen Huang ◽

Jiaozhen Zhang ◽

Min Yang ◽

Qiuchen Qi ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Therapeutic Effect ◽

Inflammatory Responses ◽

Active Ingredients ◽

Bletilla Striata ◽

Anti Inflammatory

Identification of active ingredients, and their structures, from Bletilla striata and investigation of the antioxidative and anti-inflammatory responses in vitro and in vivo.

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Corylin Ameliorates LPS-Induced Acute Lung Injury via Suppressing the MAPKs and IL-6/STAT3 Signaling Pathways

Pharmaceuticals ◽

10.3390/ph14101046 ◽

2021 ◽

Vol 14 (10) ◽

pp. 1046

Author(s):

I-Chen Chen ◽

Shu-Chi Wang ◽

Yi-Ting Chen ◽

Hsin-Han Tseng ◽

Po-Len Liu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Immune Cell ◽

Therapeutic Potential ◽

Lavage Fluid ◽

Mitogen Activated Protein ◽

Associated Proteins ◽

Anti Inflammatory

Acute lung injury (ALI) is a high mortality disease with acute inflammation. Corylin is a compound isolated from the whole plant of Psoralea corylifolia L. and has been reported to have anti-inflammatory activities. Herein, we investigated the therapeutic potential of corylin on lipopolysaccharides (LPS)-induced ALI, both in vitro and in vivo. The levels of proinflammatory cytokine secretions were analyzed by ELISA; the expressions of inflammation-associated proteins were detected using Western blot; and the number of immune cell infiltrations in the bronchial alveolar lavage fluid (BALF) were detected by multicolor flow cytometry and lung tissues by hematoxylin and eosin (HE) staining, respectively. Experimental results indicated that corylin attenuated LPS-induced IL-6 production in human bronchial epithelial cells (HBEC3-KT cells). In intratracheal LPS-induced ALI mice, corylin attenuated tissue damage, suppressed inflammatory cell infiltration, and decreased IL-6 and TNF-α secretions in the BALF and serum. Moreover, it further inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including p-JNK, p-ERK, p-p38, and repressed the activation of signal transducer and activator of transcription 3 (STAT3) in lungs. Collectively, our results are the first to demonstrate the anti-inflammatory effects of corylin on LPS-induced ALI and suggest corylin has significant potential as a novel therapeutic agent for ALI.

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Evidence That the Anti-Inflammatory Effect of Rubiadin-1-methyl Ether Has an Immunomodulatory Context

Mediators of Inflammation ◽

10.1155/2019/6474168 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12

Author(s):

Eduarda Talita Bramorski Mohr ◽

Marcus Vinicius Pereira dos Santos Nascimento ◽

Júlia Salvan da Rosa ◽

Guilherme Nicácio Vieira ◽

Iara Fabricia Kretzer ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Methyl Ether ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Inflammatory Parameters ◽

Anti Inflammatory ◽

Inflammatory Effect

Background. In spite of the latest therapeutic developments, no effective treatments for handling critical conditions such as acute lung injuries have yet been found. Such conditions, which may result from lung infections, sepsis, multiple trauma, or shock, represent a significant challenge in intensive care medicine. Seeking ways to better deal with this challenge, the scientific community has recently devoted much attention to small molecules derived from natural products with anti-inflammatory and immunomodulatory effects. Aims. In this context, we investigated the anti-inflammatory effect of Rubiadin-1-methyl ether isolated from Pentas schimperi, using an in vitro model of RAW 264.7 macrophages induced by LPS and an in vivo model of acute lung injury (ALI) induced by LPS. Methods. The macrophages were pretreated with the compound and induced by LPS (1 μg/mL). After 24 h, using the supernatant, we evaluated the cytotoxicity, NOx, and IL-6, IL-1β, and TNF-α levels, as well as the effect of the compound on macrophage apoptosis. Next, the compound was administered in mice with acute lung injury (ALI) induced by LPS (5 mg/kg), and the pro- and anti-inflammatory parameters were analyzed after 12 h using the bronchoalveolar lavage fluid (BALF). Results. Rubiadin-1-methyl ether was able to inhibit the pro-inflammatory parameters studied in the in vitro assays (NOx, IL-6, and IL-1β) and, at the same time, increased the macrophage apoptosis rate. In the in vivo experiments, this compound was capable of decreasing leukocyte infiltration; fluid leakage; NOx; IL-6, IL-12p70, IFN-γ, TNF-α, and MCP-1 levels; and MPO activity. In addition, Rubiadin-1-methyl ether increased the IL-10 levels in the bronchoalveolar lavage fluid (BALF). Conclusions. These findings support the evidence that Rubiadin-1-methyl ether has important anti-inflammatory activity, with evidence of an immunomodulatory effect.

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Alpinumisoflavone attenuates lipopolysaccharide-induced acute lung injury by regulating the effects of anti-oxidation and anti-inflammation both in vitro and in vivo

RSC Advances ◽

10.1039/c8ra04098b ◽

2018 ◽

Vol 8 (55) ◽

pp. 31515-31528 ◽

Cited By ~ 6

Author(s):

Pei-Ying Li ◽

Yu-Chia Liang ◽

Ming-Jyh Sheu ◽

Shyh-Shyun Huang ◽

Che-Yi Chao ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Model ◽

Raw264.7 Macrophages ◽

Anti Inflammatory ◽

Anti Inflammation

The present study demonstrated that alpinumisoflavone exerts the significant effects of anti-inflammatory and anti-oxidative in both LPS-induced RAW264.7 macrophages and a mouse model of acute lung injury.

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Combination Effect of Three Main Constituents From Sarcandra glabra Inhibits Oxidative Stress in the Mice Following Acute Lung Injury: A Role of MAPK-NF-κB Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2020.580064 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chun-Ping Liu ◽

Jian-Xing Liu ◽

Jiangyong Gu ◽

Fang Liu ◽

Jin-Hua Li ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Raw 264.7 Cells ◽

Anti Inflammatory ◽

Model C ◽

Raw264.7 Macrophage

Caffeoylquinic acids, coumarins and dicaffeoyl derivatives are considered to be three kinds of the most abundant bioactive components in Sarcandra glabra, an anti-inflammatory herb mainly found in Southern Asia. The combined anti-inflammatory effect of three typical constituents C + R + I (chlorogenic acid + rosmarinic acid + isofraxidin) from this plant has been investigated. The result implies that targeting the MAPK-NF-κB pathway would be one of the major mechanisms involved, using LPS stimulated RAW 264.7 cells as in vitro model and LPS-induced acute lung injury in mice as in vivo model. C + R + I can significantly suppress the levels of nitric oxide (NO), pro-inflammatory cytokines, and inhibit iNOS and COX-2 expression in LPS-treated RAW264.7 macrophage cells. Western blot analysis showed that C + R + I suppressed phosphorylation of NF-κB and MAPK, including phosphorylation of p65-NF-κB, IKB, ERK, JNK and P38. Besides, C + R + I suppressed MPO protein expression, but promoted SOD and HO-1 expression, and the related targets for C, R, and I were also predicted by molecular docking. This indicated that C + R + I could alleviate oxidative stress induced by LPS, which were further verified in the in vivo model of mice with acute lung injury through the measurement of corresponding inflammatory mediators and the analysis of immunehistochemistry.

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Celastrol alleviates LPS-induced inflammation in BMDMs and acute lung injury in mice via inhibition of p-38 MAPK/MK2 signaling

European Journal of Inflammation ◽

10.1177/20587392211020569 ◽

2021 ◽

Vol 19 ◽

pp. 205873922110205

Author(s):

Zhengxu Chen ◽

Xinyi Yang ◽

Lu Zhang ◽

Man Li ◽

Lei Sun ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

P38 Mapk ◽

Lavage Fluid ◽

Lung Edema ◽

Tnf Α ◽

Anti Inflammatory ◽

Inflammatory Effect

Objective: Celastrol is a compound extracted from a medicinal plant Tripterygium wilfordii which has a broad-spectrum anti-inflammatory effect in traditional medicine. However, the effect of celastrol on acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is still unknown. Methods: We reported that celastrol alleviated LPS-induced acute lung injury by H&E staining, MPO activity and the expression of cytokines in broncho-alveolar lavage fluid. The effect of celastrol on bone marrow-derived macrophages (BMDMs) after LPS treatment was measured by ELISA and Western blotting. Results: In vivo, celastrol reduced the LPS-induced lung edema and MPO activity of lung tissue. Furthermore, the production of inflammatory cytokines IL-6, TNF-α, and KC in bronchoalveolar lavage was reduced. In vitro, upon treatment of LPS, celastrol dose-dependently inhibited the expression of iNOS in BMDMs. Meanwhile, the expression of IL-6, TNF-α, and KC in BMDMs were also inhibited by celastrol treatment. Furthermore, we found that celastrol attenuated the phosphorylation of p38 MAPK and MK2, and inhibited the interaction between p38 MAPK and MK2. Conclusion: Our data indicate that celastrol has an anti-inflammatory effect on LPS-induced inflammatory response in vivo and in vitro, suggesting celastrol is a promising compound for the treatment of ALI and ARDS.

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