In vivo anti-inflammatory action of eugenol on lipopolysaccharide-induced lung injury

2010 ◽  
Vol 108 (4) ◽  
pp. 845-851 ◽  
Author(s):  
Clarissa B. Magalhães ◽  
Douglas R. Riva ◽  
Leonardo J. DePaula ◽  
Aline Brando-Lima ◽  
Vera Lúcia G. Koatz ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lavage Fluid ◽  
Nuclear Factor Κb ◽  
Tissue Expression ◽  
The Other ◽  
Alveolar Collapse ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Action

Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-κB (NF-κB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 μg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (ΔP1) and viscoelastic (ΔP2) pressures, static elastance (Est), and viscoelastic component of elastance (ΔE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-α was determined by ELISA. Lung tissue expression of NF-κB was determined by EMSA. ΔP1, ΔP2, Est, and ΔE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-α levels and NF-κB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.

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

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.

scholarly journals Baicalin Liposome Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Inhibiting TLR4/JNK/ERK/NF-κB Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yu Long ◽  
Yan Xiang ◽  
Songyu Liu ◽  
Yulu Zhang ◽  
Jinyan Wan ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Injury Score ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Scutellaria Baicalensis Georgi ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Novel Drug

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are challenging diseases with the high mortality in a clinical setting. Baicalin (BA) is the main effective constituent isolated from the Chinese medical herb Scutellaria baicalensis Georgi, and studies have proved that it has a protective effect on ALI induced by lipopolysaccharide (LPS) due to the anti-inflammatory efficacy. However, BA has low solubility which may limit its clinical application. Hence, we prepared a novel drug delivery system—Baicalin liposome (BA-LP) in previous research—which can improve some physical properties of BA. Therefore, we aimed to explore the effect of BA-LP on ALI mice induced by LPS. In pharmacokinetics study, the values of t 1 / 2 and AUC0- t in the BA-LP group were significantly higher than that of the BA group in normal mice, indicating that BA-LP could prolong the duration time in vivo of BA. The BA-LP group also showed a higher concentration in lung tissues than the BA group. Pharmacodynamics studies showed that BA-LP had a better effect than the BA group at the same dosage on reducing the W/D ratio, alleviating the lung injury score, and decreasing the proinflammatory factors (TNF-α, IL-1β) and total proteins in bronchoalveolar lavage fluids (BALF). In addition, the therapeutic effects of BA-LP showed a dose-dependent manner. Western blot analysis indicated that the anti-inflammatory action of BA could be attributed to the inhibition of the TLR4-NFκBp65 and JNK-ERK signaling pathways. These results suggest that BA-LP could be a valuable therapeutic candidate in the treatment of ALI.

scholarly journals HDAC2 is required by the physiological concentration of glucocorticoid to inhibit inflammation in cardiac fibroblasts

2017 ◽  
Vol 95 (9) ◽  
pp. 1030-1038 ◽  
Author(s):  
Haining Zhang ◽  
Yanhua He ◽  
Guiping Zhang ◽  
Xiaobin Li ◽  
Suikai Yan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cardiac Fibroblasts ◽  
Myocardial Inflammation ◽  
Physiological Concentration ◽  
Physiological Level ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Action

We previously suggested that endogenous glucocorticoids (GCs) may inhibit myocardial inflammation induced by lipopolysaccharide (LPS) in vivo. However, the possible cellular and molecular mechanisms were poorly understood. In this study, we investigated the role of physiological concentration of GCs in inflammation induced by LPS in cardiac fibroblasts and explored the possible mechanisms. The results showed that hydrocortisone at the dose of 127 ng/mL (equivalent to endogenous basal level of GCs) inhibited LPS (100 ng/mL)-induced productions of TNF-α and IL-1β in cardiac fibroblasts. Xanthine oxidase/xanthine (XO/X) system impaired the anti-inflammatory action of GCs through downregulating HDAC2 activity and expression. Knockdown of HDAC2 restrained the anti-inflammatory effects of physiological level of hydrocortisone, and blunted the ability of XO/X system to downregulate the inhibitory action of physiological level of hydrocortisone on cytokines. These results suggested that HDAC2 was required by the physiological concentration of GC to inhibit inflammatory response. The dysfunction of HDAC2 induced by oxidative stress might be account for GC resistance and chronic inflammatory disorders during the cardiac diseases.

scholarly journals Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative

2021 ◽  
Vol 22 (15) ◽  
pp. 8158
Author(s):  
Fatin Jannus ◽  
Marta Medina-O’Donnell ◽  
Veronika E. Neubrand ◽  
Milagros Marín ◽  
Maria J. Saez-Lara ◽  
...  
Keyword(s):  
Oleanolic Acid ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Tetradecanoyl Phorbol Acetate ◽  
Tnf Α ◽  
Effective Therapeutic Strategy ◽  
Anti Inflammatory ◽  
Inflammatory Action

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1β, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes.

scholarly journals Milonine Protects Against Acute Lung Injury By Modulating The Akt And NF-κB Signaling Pathway

2021 ◽  
Author(s):  
Larissa Rodrigues Bernardo ◽  
Laércia Karla Diega Paiva Ferreira ◽  
Larissa Adilis Maria Paiva Ferreira ◽  
Cosmo Isaías Duvirgens Vieira ◽  
João Batista de Oliveira ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Hydrophobic Interactions ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Lung Edema ◽  
Toll Like Receptor 4 ◽  
Downstream Signaling ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Acute lung injury (ALI) is an inflammation that triggers acute respiratory distress syndrome (ARDS) with perialveolar neutrophil infiltration, alveolar-capillary barrier damage, and lung edema. Activation of the toll-like receptor 4 complex and its downstream signaling pathways are responsible for the cytokine storm and cause alveolar damage on ARDS. Due to the complexity of inflammatory events on ALI, a defined pharmacotherapy has not been established. Thus, this study aimed to evaluate the anti-inflammatory potential of milonine, an alkaloid of Cissampelos sympodialis Eichl, in an ALI experimental model. BALB/c mice were lipopolysaccharide (LPS)-challenged and treated with milonine at 2.0 mg/kg. Twenty-four hours later, the bronchoalveolar lavage fluid (BALF), peripheral blood, and lungs were collected for cellular and molecular analysis. The milonine treatment decreased the inflammatory cell migration (principally neutrophils) to the alveolar cavity, the protein exudate, the pulmonary edema, and the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) into the BALF. The systemic level of IL-6 level was also reduced. In the lung tissue, milonine reduced the bronchoalveolar damage. The milonine docking analyzes demonstrated that the molecule formed hydrophobic interactions with the amino-acids Ile124 and Phe126 of the TLR4/MD2 groove. Indeed, the anti-inflammatory effect of milonine was due to the negative regulation of cytoplasmic kinase-Akt and NF-κB by interacting with the TLR4/MD2 complex. Therefore, milonine is an effective inflammatory modulator by blocking the interaction of the LPS-TLR4/MD2 complex and downregulating the intracellular inflammatory pathway axis being a potential molecule for the treatment of ALI.

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

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.

Pneumocystis carinii infection sensitizes lung to radiation-induced injury after syngeneic marrow transplantation: role of CD4+ T cells

2006 ◽  
Vol 290 (6) ◽  
pp. L1087-L1096 ◽  
Author(s):  
Lauren Bruckner ◽  
Francis Gigliotti ◽  
Terry Wright ◽  
Allen Harmsen ◽  
Robert H. Notter ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Injury ◽  
Pneumocystis Carinii ◽  
Lavage Fluid ◽  
Marrow Transplant ◽  
Lung Compliance ◽  
Pulmonary Dysfunction ◽  
Tnf Α ◽  
Total Body

A murine model of bone marrow transplant (BMT)-related lung injury was developed to study how infection sensitizes lung to the damaging effects of total body irradiation (TBI) at infectious and TBI doses that individually do not cause injury. Mice infected with Pneumocystis carinii exhibited an asymptomatic, rapid, and transient influx of eosinophils and T cells in bronchoalveolar lavage fluid (BALF). In contrast, mice infected with P. carinii 7 days before receiving TBI and syngeneic BMT ( P. carinii/TBI mice) exhibited severe pulmonary dysfunction, surfactant aggregate depletion, and surfactant activity reductions at 17 days post-BMT. BALF from P. carinii/TBI mice contained a disproportionate initial influx of CD4+ T cells (CD4+:CD8+ ratio of 2.7) that correlated with progressive lung injury (from 8 to 17 days post-BMT). Levels of TNF-α in BALF were significantly increased in P. carinii/TBI mice compared with mice given either insult alone, with peak values found at 11 days post-BMT. In vivo depletion of CD4+ T cells in P. carinii/TBI mice abrogated pulmonary dysfunction and reduced TNF-α levels in BALF, whereas depletion of CD8+ T cells did not affect lung compliance or TNF-α. Lung injury was not attributable to direct P. carinii damage, since CD4-depleted P. carinii/TBI mice that exhibited no injury had higher average lung P. carinii burdens than either mice given P. carinii alone or undepleted P. carinii/TBI mice. Together, these results indicate that P. carinii infection can sensitize the lung to subsequent TBI-mediated lung injury via a process dependent on non-alloreactive CD4+ T cells.

scholarly journals Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1532
Author(s):  
Eui-Baek Byun ◽  
Ha-Yeon Song ◽  
Woo Sik Kim ◽  
Jeong Moo Han ◽  
Ho Seong Seo ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Tlr Signaling ◽  
Induced Expression ◽  
Interacting Protein ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Action

Although our previous study revealed that gamma-irradiated chrysin enhanced anti-inflammatory activity compared to intact chrysin, it remains unclear whether the chrysin derivative, CM1, produced by gamma irradiation, negatively regulates toll-like receptor (TLR) signaling. In this study, we investigated the molecular basis for the downregulation of TLR4 signal transduction by CM1 in macrophages. We initially determined the appropriate concentration of CM1 and found no cellular toxicity below 2 μg/mL. Upon stimulation with lipopolysaccharide (LPS), CM1 modulated LPS-stimulated inflammatory action by suppressing the release of proinflammatory mediators (cytokines TNF-α and IL-6) and nitric oxide (NO) and downregulated the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, CM1 markedly elevated the expression of the TLR negative regulator toll-interacting protein (Tollip) in dose- and time-dependent manners. LPS-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II), proinflammatory cytokines (TNF-α and IL-6), COX-2, and iNOS-mediated NO were inhibited by CM1; these effects were prevented by the knockdown of Tollip expression. Additionally, CM1 did not affect the downregulation of LPS-induced expression of MAPKs and NF-κB signaling in Tollip-downregulated cells. These findings provide insight into effective therapeutic intervention of inflammatory disease by increasing the understanding of the negative regulation of TLR signaling induced by CM1.

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

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.

scholarly journals Comparison of Anti-Inflammatory Activities of Structurally Similar Triterpenoids Isolated from Bitter Melon

2017 ◽  
Vol 12 (12) ◽  
pp. 1934578X1701201
Author(s):  
Hsueh-Ling Cheng ◽  
Ming-Hao Yang ◽  
Rista Anggriani ◽  
Chi-I Chang
Keyword(s):  
Nuclear Factor Κb ◽  
Inos Expression ◽  
Inflammatory Activity ◽  
Bitter Melon ◽  
Jun Kinase ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Oxide Synthase

Momordica charantia L., or bitter melon, has been suggested to exhibit anti-inflammatory activity. In a previous study, three structurally similar triterpenes, namely 5β,19-epoxy-25-methoxycucurbita-6,23-diene-3β,19-diol (EMCD), 5β,19-epoxy-25-methoxycucurbita-6,23-dien-3β-ol (EMCO), and 5β,19-epoxy-19,25-dimethoxycucurbita-6,23-dien-3β-ol (EDMO), were isolated from bitter melon. EMCD has been shown to exhibit in vitro anti-inflammatory activity. In this study, the anti-inflammatory activities of EMCD, EMCO, and EDMO were compared. All three compounds were toxic to the RAW 264.7 macrophage cell line but not the FL83B cells. EMCD and EMCO inhibited tumor necrosis factor (TNF)-α-induced inducible nitric oxide synthase (iNOS) expression in FL83B cells, and the IC50 values were 19.8 and 25.7 μM, respectively. By contrast, EDMO did not effectively reduce iNOS expression. Furthermore, EMCD and EMCO suppressed other TNF-α-induced proinflammatory signals including the activation of inhibitor kappa B kinase complex, the phosphorylation of inhibitor of nuclear factor-κB, and the activation of c-Jun kinase. EMCD consistently exhibited a higher efficacy than did EMCO in these assays. Hence, the in vivo anti-inflammatory activity of EMCD was tested. EMCD clearly repressed 12- O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. In conclusion, differences in the functional group on carbon 19 do affect the anti-inflammatory activities of EMCD, EMCO, and EDMO. EMCD exhibited the highest anti-inflammatory activity among these molecules, and its in vivo anti-inflammatory activity was confirmed.

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