Anti-inflammatory effects of celecoxib in rat lungs with smoke-induced emphysema

2010 ◽  
Vol 299 (2) ◽  
pp. L184-L191 ◽  
Author(s):  
Gu Seob Roh ◽  
Chin-ok Yi ◽  
Yu Ji Cho ◽  
Byeong Tak Jeon ◽  
Irina Tsoy Nizamudtinova ◽  
...  
Keyword(s):  
Pulmonary Emphysema ◽  
Pulmonary Inflammation ◽  
Inhibitory Effect ◽  
No Production ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Rat Lungs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Regulated Gene Expression

Chronic airway inflammation is a characteristic feature of destructive cigarette smoking (CS)-induced lung disease, particularly in patients with emphysema. Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is widely used to treat inflammation. However, the exact mechanisms underlying this drug's anti-inflammatory effects have not yet been determined in pulmonary emphysema. Here, we explore whether celecoxib attenuates CS-induced inflammation in rat lungs. Rats were exposed to smoke and received celecoxib via intragastric feeding daily for 20 wk. We found that celecoxib inhibited interalveolar wall distance and pulmonary inflammation in the lungs of CS-treated rats. Celecoxib inhibited serum NO production, iNOS, COX-2 expression, and PGE2 production in CS-treated lung tissues. Our immunohistochemical data showed that CS-induced CD68 and COX-2 expression were inhibited by celecoxib. Furthermore, celecoxib attenuated the activation of phospho-IκBα and NF-κB in CS-treated rat lung. In addition, there was an inhibitory effect of celecoxib on the COX-2 expression and NF-κB activation in LPS-stimulated RAW 264.7 macrophages. Celecoxib also attenuated NF-κB activation in COX-2 siRNA-transfected RAW 264.7 macrophages. Thus, our findings suggest that the anti-inflammatory effects of celecoxib are mediated by its effects on NF-κB-regulated gene expression, which ultimately reduces the progression of CS-induced pulmonary emphysema.

scholarly journals Evaluation of the Inhibitory Effects of Pyridylpyrazole Derivatives on LPS-Induced PGE2 Productions and Nitric Oxide in Murine RAW 264.7 Macrophages

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6489
Author(s):  
Mahmoud M. Gamal El-Din ◽  
Mohammed I. El-Gamal ◽  
Young-Do Kwon ◽  
Su-Yeon Kim ◽  
Hee-Soo Han ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
No Production ◽  
Raw 264.7 ◽  
Inhibitory Effects ◽  
Western Blots ◽  
Raw 264.7 Macrophages ◽  
Inos Protein Expression ◽  
Ic50 Values ◽  
Cox 2

A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds 1a–m have first been assessed for cytotoxicity against RAW 264.7 macrophages to determine their non-cytotoxic concentration(s) for anti-inflammatory testing to make sure that the inhibition of PGE2 and NO production would not be caused by cytotoxicity. It was found that compounds 1f and 1m were the most potent PGE2 inhibitors with IC50 values of 7.1 and 1.1 μM, respectively. In addition, these compounds also showed inhibitory effects of 11.6% and 37.19% on LPS-induced NO production, respectively. The western blots analysis of COX-2 and iNOS showed that the PGE2 and NO inhibitory effect of compound 1m are attributed to inhibition of COX-2 and iNOS protein expression through inactivation of p38.

scholarly journals (3β,16α)-3,16-Dihydroxypregn-5-en-20-one from the Twigs of Euonymus alatus (Thunb.) Sieb. Exerts Anti-Inflammatory Effects in LPS-Stimulated RAW-264.7 Macrophages

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3848 ◽  
Author(s):  
Seulah Lee ◽  
Dahae Lee ◽  
Su Cheol Baek ◽  
Mun Seok Jo ◽  
Ki Sung Kang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Medicinal Plant ◽  
Phytochemical Analysis ◽  
No Production ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Euonymus Alatus ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Pharmacologically Active

To discover new pharmacologically active natural products, here, we performed the phytochemical analysis of a Korean medicinal plant. Euonymus alatus (Thunb.) Sieb. is a traditional medicinal plant that has been used as a remedy for various diseases in Asian countries. In particular, the cork cambium on the twigs of E. alatus has been used to treat dysmenorrhea, tumors, diabetes, and wound. Phytochemical analysis of the methanolic extract of E. alatus twigs led to the isolation of a sterol, which was identified as (3β,16α)-3,16-dihydroxypregn-5-en-20-one (1) by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry. The stereochemistry of 1 was established with nuclear Overhauser effect spectroscopy (NOESY) analysis and comparison of electronic circular dichroism (ECD) data. To the best of our knowledge, the isolation of compound 1 from nature is first reported here, as well as the complete and revised NMR data assignment of 1. In lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages, compound 1 significantly inhibited nitric oxide (NO) production at an IC50 value of 12.54 ± 0.05 μM as well as the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, the pre-treatment with compound 1 attenuated the LPS-induced phosphorylation of nuclear factor kappa B (NF-κB) p65 through the inhibition of the phosphorylation of IκB kinase alpha (IKKα), IKKβ, and inhibitor of kappa B alpha (IκBα). Compound 1 also inhibited the LPS-induced phosphorylation of p38, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Taken together, compound 1 may serve as an anti-inflammatory constituent of E. alatus twigs and its anti-inflammatory property is thought to be associated with the inhibition of NO production via suppression of iNOS and COX-2 expression through inhibition of IKKα/β, I-κBα and NF-κB p65 activation and downregulation of p38, JNK, and ERK mitogen-activated protein kinase signal pathways in RAW 264.7 macrophages. These findings also provide experimental evidence that compound 1 identified from E. alatus twigs could be a candidate for an anti-inflammatory agent.

scholarly journals Protective Effect of Membrane-Free Stem Cells against Lipopolysaccharide and Interferon-Gamma-Stimulated Inflammatory Responses in RAW 264.7 Macrophages

2021 ◽  
Vol 22 (13) ◽  
pp. 6894
Author(s):  
Mei Tong He ◽  
Hye Sook Park ◽  
Young Sil Kim ◽  
Ah Young Lee ◽  
Eun Ju Cho
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Interferon Gamma ◽  
Mapk Signaling ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Protein Expressions ◽  
Ifn Γ ◽  
Cox 2 ◽  
Anti Inflammatory

Recently, adipose-derived stem cells (ADSCs) are considered to be ideal for application in cell therapy or tissue regeneration, mainly due to their wide availability and easy access. In this study, we examined the anti-inflammatory effects of membrane-free stem cell extract (MFSC-Ex) derived from ADSCs against lipopolysaccharide (LPS)/interferon-gamma (IFN-γ) on RAW 264.7 macrophage cells. Exposure of RAW macrophages to LPS and IFN-γ stimuli induced high levels of nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) production. However, pretreatment with MFSC-Ex inhibited LPS/IFN-γ-induced these pro-inflammatory mediators. To clarify the molecular mechanisms underlying the anti-inflammatory property of MFSC-Ex, we analyzed nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) protein expressions by Western blotting. Our study showed that treatment of MFSC-Ex significantly down-regulated inducible nitric oxide synthase (iNOS) and COX-2 protein expressions. Furthermore, phosphorylation of extracellular signal-regulated kinase (ERK) and p38 was also blocked by treatment with MFSC-Ex, indicating that inhibitory effect of MFSC-Ex on MAPK signaling cascade may attribute to inactivation of NF-κB. From these findings, we suggest that MFSC-Ex exert anti-inflammatory activities, which suppressed LPS/IFN-γ-induced production of NO, COX-2 and PGE2 by regulation of NF-κB and MAPK signaling pathway in RAW 264.7 macrophages. In conclusion, MFSC-Ex might provide a new therapeutic opportunity to treatment of inflammatory-related diseases.

scholarly journals The Remarkable Antioxidant and Anti-Inflammatory Potential of the Extracts of the Brown Alga Cystoseira amentacea var. stricta

Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 2
Author(s):  
Gina De La Fuente ◽  
Marco Fontana ◽  
Valentina Asnaghi ◽  
Mariachiara Chiantore ◽  
Serena Mirata ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
No Production ◽  
Low Grade ◽  
Raw 264.7 ◽  
Ros Scavenging ◽  
Ligurian Sea ◽  
Raw 264.7 Macrophages ◽  
Pharmaceutical Industries ◽  
Anti Inflammatory ◽  
First Time

Inflammation and oxidative stress are part of the complex biological responses of body tissues to harmful stimuli. In recent years, due to the increased understanding that oxidative stress is implicated in several diseases, pharmaceutical industries have invested in the research and development of new antioxidant compounds, especially from marine environment sources. Marine seaweeds have shown the presence of many bioactive secondary metabolites, with great potentialities from both the nutraceutical and the biomedical point of view. In this study, 50%-ethanolic and DMSO extracts from the species C. amentacea var. stricta were obtained for the first time from seaweeds collected in the Ligurian Sea (north-western Mediterranean). The bioactive properties of these extracts were then investigated, in terms of quantification of specific antioxidant activities by relevant ROS scavenging spectrophotometric tests, and of anti-inflammatory properties in LPS-stimulated macrophages by evaluation of inhibition of inflammatory cytokines and mediators. The data obtained in this study demonstrate a strong anti-inflammatory effect of both C. amentacea extracts (DMSO and ethanolic). The extracts showed a very low grade of toxicity on RAW 264.7 macrophages and L929 fibroblasts and a plethora of antioxidant and anti-inflammatory effects that were for the first time thoroughly investigated. The two extracts were able to scavenge OH and NO radicals (OH EC50 between 392 and 454 μg/mL; NO EC50 between 546 and 1293 μg/mL), to partially rescue H2O2-induced RAW 264.7 macrophages cell death, to abate intracellular ROS production in H2O2-stimulated macrophages and fibroblasts and to strongly inhibit LPS-induced inflammatory mediators, such as NO production and IL-1α, IL-6, cyclooxygenase-2 and inducible NO synthase gene expression in RAW 264.7 macrophages. These results pave the way, for the future use of C. amentacea metabolites, as an example, as antioxidant food additives in antiaging formulations as well as in cosmetic lenitive lotions for inflamed and/or damaged skin.

Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Zafer Sahin ◽  
Yağmur Özhan ◽  
Hande Sipahi ◽  
Sevde Nur Biltekin ◽  
Leyla Yurttaş ◽  
...  
Keyword(s):  
Hydroxy Ketone ◽  
No Production ◽  
Raw 264.7 ◽  
Pyrazole Derivatives ◽  
H Nmr ◽  
Pyrazolone Derivatives ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1 ◽  
C Nmr

Abstract Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with α-hydroxy aldehyde or α-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by 1H NMR, 13C NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0 μM and 8.0 μM IC50, respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 μM IC50. Rest of the compounds (1, 3–9) showed 10.4–28.1 μM IC50 on COX-2 and 17.0–35.6 μM IC50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds (1–9) showed activity on NO production. Only compound was the 4, which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100 μM for all compounds (1–9) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic.

Fermentation Improves Anti-Inflammatory Effect of Sipjeondaebotang on LPS-Stimulated RAW 264.7 Cells

2012 ◽  
Vol 40 (04) ◽  
pp. 813-831 ◽  
Author(s):  
You-Chang Oh ◽  
Won-Kyung Cho ◽  
Yun Hee Jeong ◽  
Ga Young Im ◽  
Min Cheol Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
High Performance ◽  
Biological Effects ◽  
Inhibitory Effect ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Sipjeondaebotang (SJ) has been used as a traditional drug in east-Asian countries. In this study, to provide insight into the biological effects of SJ and SJ fermented by Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in macrophages. The investigation was focused on whether SJ and fermented SJ could inhibit the production of pro-inflammatory mediators such as prostaglandin (PG) E2 and nitric oxide (NO) as well as the expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in LPS-stimulated RAW 264.7 cells. We found that SJ modestly inhibited LPS-induced PGE2, NO and TNF-α production as well as the expressions of COX-2 and iNOS. Interestingly, fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, fermented SJ exhibited increased inhibition of p38 MAPK and c-Jun NH2-terminal kinase (JNK) MAPK phosphorylation as well as NF-κB p65 translocation by reduced IκBα degradation compared with either untreated controls or unfermented SJ. High performance liquid chromatography (HPLC) analysis showed fermentation by Lactobacillus increases liquiritigenin and cinnamyl alcohol contained in SJ, which are known for their anti-inflammatory activities. Finally, SJ fermented by Lactobacillus exerted potent anti-inflammatory activity by inhibiting MAPK and NF-κB signaling in RAW 264.7 cells.

scholarly journals Enhanced anti-inflammatory effect of resveratrol and EPA in treated endotoxin-activated RAW 264.7 macrophages

2012 ◽  
Vol 108 (9) ◽  
pp. 1562-1573 ◽  
Author(s):  
Victor Pallarès ◽  
Damien Calay ◽  
Lídia Cedó ◽  
Anna Castell-Auví ◽  
Martine Raes ◽  
...  
Keyword(s):  
Epigallocatechin Gallate ◽  
No Production ◽  
Raw 264.7 ◽  
Fish Food ◽  
Antioxidant Genes ◽  
Raw 264.7 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Macrophages play an important role in immunogenic challenges by producing reactive oxygen species, NO and proinflammatory cytokines that can aggravate and propagate local inflammation. Multiple mechanisms regulate these inflammatory processes. NF-κB and activator protein 1 pathways are crucial in the expression of proinflammatory genes, such as TNF-α, IL-1 (α or β) and -6. Some polyphenols, which are present in beverages, vegetables and fruits, and PUFA, which are present in marine oils and fish food, possess anti-inflammatory effects in vivo and in vitro. Our aim in the present study was to assess whether polyphenols and PUFA have synergistic anti-inflammatory effects in murine macrophages in vitro. Inflammation in RAW 264.7 macrophages was induced by lipopolysaccharide at 100 ng/ml. The treatments with molecules were performed by co-incubation for 19 h. A NO production assay by Griess reaction, a phosphoprotein assay by Pathscan ELISA kit and gene expression analysis using the TaqMan® Low-density Array for ninety-one genes related to inflammation, oxidative stress and metabolism were performed to assess the synergistic anti-inflammatory effects of polyphenols, epigallocatechin gallate and resveratrol (Res; 2·5 μg/ml), and the PUFA, DHA and EPA (30 μm). Adding Res+EPA had an enhanced anti-inflammatory effect, in comparison with EPA and Res alone, leading to decreased NO levels; modulating the phospho-stress activated protein kinase/Jun N-terminal kinase (P-SAPK/JNK) level; down-regulating proinflammatory genes, such as IL, chemokines, transcription factors; and up-regulating several antioxidant genes. Therefore, this combination has a stronger anti-inflammatory effect than either of these molecules separately in RAW macrophages.

scholarly journals Auraptene, a Monoterpene Coumarin, Inhibits LTA-Induced Inflammatory Mediators via Modulating NF-κB/MAPKs Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Chih-Hsuan Hsia ◽  
Thanasekaran Jayakumar ◽  
Wan-Jung Lu ◽  
Joen-Rong Sheu ◽  
Chih-Wei Hsia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Nuclear Translocation ◽  
Polyacrylamide Gel Electrophoresis ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Objective. Oxidative stress-mediated inflammatory events involve in the progress of several diseases such as asthma, cancers, and multiple sclerosis. Auraptene (AU), a natural prenyloxycoumarin, possesses numerous pharmacological activities. Here, the anti-inflammatory effects of AU were investigated in lipoteichoic acid- (LTA-) induced macrophage cells (RAW 264.7). Methods. The expression of cyclooxygenase (COX-2), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) and the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, c-Jun N-terminal kinase (JNK), heme oxygenase (HO-1), p65, and IκBα were all identified by western blotting assay. The level of nitric oxide (NO) was measured by spectrometer analysis. The nuclear translocation of p65 nuclear factor kappa B (NF-κB) was assessed by the confocal microscopic staining method. Native polyacrylamide gel electrophoresis was performed to perceive the activity of antioxidant enzyme catalase (CAT). Results. AU expressively reduced NO production and COX-2, TNF-α, IL-1 β, and iNOS expression in LTA-stimulated cells. AU at higher concentration (10 µM) inhibited ERK and JNK, but not p38 phosphorylation induced by LTA. Moreover, AU blocked IκB and p65 phosphorylation, and p65 nuclear translocation. However, AU pretreatment was not effective on antioxidant HO-1 expression, CAT activity, and reduced glutathione (GSH, a nonenzymatic antioxidant), in LTA-induced RAW 264.7 cells. Conclusion. The findings of this study advocate that AU shows anti-inflammatory effects via reducing NF-κB/MAPKs signaling pathways.

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