scholarly journals IRAK1/4-Targeted Anti-Inflammatory Action of Caffeic Acid

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Woo Seok Yang ◽  
Deok Jeong ◽  
Young-Su Yi ◽  
Jae Gwang Park ◽  
Hyohyun Seo ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
Nuclear Translocation ◽  
Biological Activities ◽  
Kinase Assay ◽  
Raw264.7 Cells ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Action Mechanism ◽  
Anti Inflammatory ◽  
Inflammatory Action

Caffeic acid (CA) is a phenolic compound that is frequently present in fruits, grains, and dietary supplements. Although CA has been reported to display various biological activities such as anti-inflammatory, anti-cancer, anti-viral, and anti-oxidative effects, the action mechanism of CA is not yet fully elucidated. In this study, the anti-inflammatory action mechanism of CA was examined in lipopolysaccharide (LPS) treated macrophages (RAW264.7 cells) and HCl/EtOH-induced gastritis. CA was found to diminish nitric oxide (NO) and prostaglandin E2(PGE2) production in LPS-stimulated RAW264.7 cells. Additionally, mRNA levels of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and inducible NO synthase (iNOS) were downregulated by CA. CA also strongly suppressed the nuclear translocation of AP-1 family proteins and the related upstream signaling cascade composed of interleukin-1 receptor-associated kinase 1 (IRAK1), IRAK4, TGF-β-activated kinase 1 (TAK1), mitogen-activated protein kinase kinase 4/7 (MKK4/7), and c-Jun N-terminal kinase (JNK). In a direct kinase assay, CA was revealed to directly inhibit IRAK1 and IRAK4. CA also ameliorated HCl/EtOH-induced gastric symptoms via the suppression of JNK, IRAK1, and IRAK4. Therefore, our data strongly suggest that CA acts as an anti-inflammatory drug by directly suppressing IRAK1 and IRAK4.

scholarly journals ATP-Binding Pocket-Targeted Suppression of Src and Syk by Luteolin Contributes to Its Anti-Inflammatory Action

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jeong-Oog Lee ◽  
Deok Jeong ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho
Keyword(s):  
Nuclear Translocation ◽  
Binding Pocket ◽  
Luciferase Reporter ◽  
Prostaglandin E ◽  
Atp Binding ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
Anti Inflammatory ◽  
Inflammatory Action ◽  
Artemisia Asiatica

Luteolin is a flavonoid identifiedas a major anti-inflammatory componentofArtemisia asiatica. Numerous reports have demonstrated the ability of luteolin to suppress inflammation in a variety of inflammatory conditions. However, its exact anti-inflammatory mechanism has not been fully elucidated. In the present study, the anti-inflammatory mode of action in activated macrophages of luteolin fromArtemisia asiaticawas examined by employing immunoblotting analysis, a luciferase reporter gene assay, enzyme assays, and an overexpression strategy. Luteolin dose-dependently inhibited the secretion of nitric oxide (NO) and prostaglandin E2(PGE2) and diminished the levels of mRNA transcripts of inducible NO synthase (iNOS), tumor necrosis factor- (TNF-)α, and cyclooxygenase-2 (COX-2) in lipopolysaccharide- (LPS-) and pam3CSK-treated macrophage-like RAW264.7 cells without displaying cytotoxicity. Luteolin displayed potent NO-inhibitory activity and also suppressed the nuclear translocation of NF-κB (p65 and p50) via blockade of Src and Syk, but not other mitogen-activated kinases. Overexpression of wild type Src and point mutants thereof, and molecular modelling studies, suggest that the ATP-binding pocket may be the luteolin-binding site in Src. These results strongly suggest that luteolin may exert its anti-inflammatory action by suppressing the NF-κB signaling cascade via blockade of ATP binding in Src and Syk.

scholarly journals Gymnema inodorum (Lour.) Decne. Extract Alleviates Oxidative Stress and Inflammatory Mediators Produced by RAW264.7 Macrophages

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Benjawan Dunkhunthod ◽  
Chutima Talabnin ◽  
Mark Murphy ◽  
Kanjana Thumanu ◽  
Patcharawan Sittisart ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Antioxidant Properties ◽  
Raw264.7 Cells ◽  
Mrna Levels ◽  
Ros Production ◽  
Raw264.7 Macrophages ◽  
Ifn Γ ◽  
Anti Inflammatory

Gymnema inodorum (Lour.) Decne. (G. inodorum) is widely used in Northern Thai cuisine as local vegetables and commercial herb tea products. In the present study, G. inodorum extract (GIE) was evaluated for its antioxidant and anti-inflammatory effects in LPS plus IFN-γ-induced RAW264.7 cells. Major compounds in GIE were evaluated using GC-MS and found 16 volatile compounds presenting in the extract. GIE exhibited antioxidant activity by scavenging the intracellular reactive oxygen species (ROS) production and increasing superoxide dismutase 2 (SOD2) mRNA expression in LPS plus IFN-γ-induced RAW264.7 cells. GIE showed anti-inflammatory activity through suppressing nitric oxide (NO), proinflammatory cytokine production interleukin 6 (IL-6) and also downregulation of the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6 mRNA levels in LPS plus IFN-γ-induced RAW264.7 cells. Mechanism studies showed that GIE suppressed the NF-κB p65 nuclear translocation and slightly decreased the phosphorylation of NF-κB p65 (p-NF-κB p65) protein. Our studies applied the synchrotron radiation-based FTIR microspectroscopy (SR-FTIR), supported by multivariate analysis, to identify the FTIR spectral changes based on macromolecule alterations occurring in RAW264.7 cells. SR-FTIR results demonstrated that the presence of LPS plus IFN-γ in RAW264.7 cells associated with the increase of amide I/amide II ratio (contributing to the alteration of secondary protein structure) and lipid content, whereas glycogen and other carbohydrate content were decreased. These findings lead us to believe that GIE may prevent oxidative damage by scavenging intracellular ROS production and activating the antioxidant gene, SOD2, expression. Therefore, it is possible that the antioxidant properties of GIE could modulate the inflammation process by regulating the ROS levels, which lead to the suppression of proinflammatory cytokines and genes. Therefore, GIE could be developed into a novel antioxidant and anti-inflammatory agent to treat and prevent diseases related to oxidative stress and inflammation.

scholarly journals α-Lipoic Acid Potentiates the Anti-Inflammatory Activity of Avocado/Soybean Unsaponifiables in Chondrocyte Cultures

Cartilage ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Carmelita G. Frondoza ◽  
Lowella V. Fortuno ◽  
Mark W. Grzanna ◽  
Stacy L. Ownby ◽  
Angela Y. Au ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Nuclear Factor Kappa B ◽  
Nuclear Translocation ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Nuclear Factor ◽  
Chondrocyte Cultures ◽  
Potent Inhibitory Effect ◽  
Anti Inflammatory ◽  
Pharmacologic Treatments

Objective Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) control media, (2) ASU, (3) LA, or (4) ASU + LA combination. Cells were activated with lipopolysaccharide (LPS), interleukin 1β (IL-1β) or hydrogen peroxide (H2O2) for 24 hours and supernatants were immunoassayed for PGE2. Nuclear factor-kappa B (NF-κB) analyses were performed by immunocytochemistry and Western blot following 1 hour of activation with IL-1β. Results LPS, IL-1β, or H2O2 significantly increased PGE2 production. ASU or LA alone suppressed PGE2 production in LPS and IL-1β activated cells. Only LA alone at 2.5 µg/mL was inhibitory in H2O2-activated chondrocytes. ASU + LA inhibited more than either agent alone in all activated cells. ASU + LA also inhibited the IL-1β induced nuclear translocation of NF-κB. Conclusions The present study provides evidence that chondrocyte PGE2 production can be inhibited by the combination of ASU + LA more effectively than either ASU or LA alone. Inhibition of PGE2 production is associated with the suppression of NF-κB translocation. The potent inhibitory effect of ASU + LA on PGE2 production could offer a potential advantage for a combination anti-inflammatory/antioxidant approach in the management of OA.

scholarly journals MiR-155/GSK-3β mediates anti-inflammatory effect of Chikusetsusaponin IVa by inhibiting NF-κB signaling pathway in LPS-induced RAW264.7 cell

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Xin ◽  
Qin Yuan ◽  
Chaoqi Liu ◽  
Changcheng Zhang ◽  
Ding Yuan
Keyword(s):  
Signaling Pathway ◽  
Mouse Liver ◽  
Inflammatory Responses ◽  
Biological Activities ◽  
Raw264.7 Cells ◽  
Inflammation Model ◽  
Raw264.7 Cell ◽  
Anti Inflammatory ◽  
Gsk 3Β ◽  
Inflammatory Effect

Abstract It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities. Herein, using LPS to establish acute inflammation model of mouse liver and cell line inflammation model, we investigated whether miR-155/GSK-3β regulated NF-κB signaling pathway, and CsIVa exerted anti-inflammatory effects by regulating miR-155/GSK-3β signaling pathway. Our results showed that LPS induced high expression of miR-155 and miR-155 promoted macrophage activation through GSK-3β. In addition, CsIVa inhibited inflammatory responses in LPS-induced mouse liver and RAW264.7 cells. Furthermore, we demonstrated that CsIVa improved the inflammatory response in LPS-induced RAW264.7 cells by inhibiting miR-155, increasing GSK-3β expression, and inhibiting NF-κB signaling pathway. In conclusion, our study reveals that CsIVa suppresses LPS-triggered immune response by miR-155/GSK-3β-NF-κB signaling pathway.

scholarly journals Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2032
Author(s):  
Vishnu Raj ◽  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Sanjana Chandran ◽  
Shreesh K. Ojha ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
In Vitro Models ◽  
Mrna Levels ◽  
Colonic Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

Anti-Inflammatory Effects of Canavalia gladiata in Macrophage Cells and DSS-Induced Colitis Mouse Model

2019 ◽  
Vol 47 (07) ◽  
pp. 1571-1588
Author(s):  
Hwa-Jeong Lee ◽  
Jung Up Park ◽  
Rui Hong Guo ◽  
Bok Yun Kang ◽  
In-Kyu Park ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Interleukin 1 ◽  
Raw264.7 Cells ◽  
Mice Model ◽  
Macrophage Cells ◽  
Canavalia Gladiata ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Peritoneal Macrophage Cells

Canavalia gladiata, known as sword bean, has been used as a Chinese traditional medicine for anti-inflammatory effects. However, the action mechanisms of sword bean have not yet been clearly defined. In the present study, the whole parts of a ripened sword bean (RSB) and the green sword bean (GSB) containing bean pod were extracted with ethanol by reflux extraction. The two crude extracts (RSBE and GSBE) from RSB and GSB were validated by a liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis of gallic acid as a reference chemical. The anti-inflammatory effects of two sword bean extracts were extensively investigated using LPS-stimulated macrophage cells. First, RSBE and GSBE significantly inhibited the production of pro-inflammatory mediators, such as tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-6 (IL-6), prostaglandinE2 (PGE2), and nitric oxide (NO) in LPS-induced RAW264.7 cells. RSBE and GSBE showed no cytotoxicity to RAW264.7 cells and mouse peritoneal macrophage cells. In addition, the overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) induced by LPS in RAW264.7 cells was significantly decreased by RSBE and GSBE. Western blotting and immunostaining analysis showed that RSBE and GSBE inhibited the nuclear translocation of NF-[Formula: see text]B subunits, which correlated with the inhibitory effects on inhibitor kappa B (I[Formula: see text]B) degradation. In dextran sulfated sodium (DSS)-induced colitis mice model, RSBE restored body weight, colon length, and the levels of pro-inflammatory cytokines, such as TNF-[Formula: see text], IL-6, interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interferon-[Formula: see text] (IFN-[Formula: see text]). In addition, RSBE significantly suppressed the expression of COX-2, iNOS, and NF-[Formula: see text]B.

Ethanol Extract of Lilium Bulbs Plays an Anti-Inflammatory Role by Targeting the IKKα/β-Mediated NF-κB Pathway in Macrophages

2018 ◽  
Vol 46 (06) ◽  
pp. 1281-1296 ◽  
Author(s):  
Sang Yun Han ◽  
Young-Su Yi ◽  
Seong-Gu Jeong ◽  
Yo Han Hong ◽  
Kang Jun Choi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Inflammatory Activity ◽  
Raw264.7 Cells ◽  
No Production ◽  
Dependent Manner ◽  
Bioactive Components ◽  
Anti Inflammatory

Lilium bulbs have long been used as Chinese traditional medicines to alleviate the symptoms of various human inflammatory diseases. However, mechanisms of Lilium bulb-mediated anti-inflammatory activity and the bioactive components in Lilium bulbs remain unknown. In the present study, the anti-inflammatory activity of Lilium bulbs and the underlying mechanism of action were investigated in macrophages using Lilium bulb ethanol extracts (Lb-EE). In a dose-dependent manner, Lb-EE inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs) without causing significant cytotoxicity. Lb-EE also down-regulated mRNA expression of inflammatory genes in LPS-stimulated RAW264.7 cells, which included inducuble nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]). Furthermore, Lb-EE markedly restored LPS-induced morphological changes in RAW264.7 cells to a normal morphology. HPLC analysis identified quercetin, luteolin, and kaempferol as bioactive components contained in Lb-EE. Mechanistic studies in LPS-stimulated RAW264.7 cells revealed that Lb-EE suppressed MyD88- and TRIF-induced NF-[Formula: see text]B transcriptional activation and the nuclear translocation of NF-[Formula: see text]B transcription factors. Moreover, Lb-EE inhibited IKK[Formula: see text]/[Formula: see text]-induced activation of the NF-[Formula: see text]B signaling pathway and IKK inhibition significantly reduced NO production in LPS-stimulated RAW264.7 cells. Taken together, these results suggest that Lb-EE plays an anti-inflammatory role by targeting IKK[Formula: see text]/[Formula: see text]-mediated activation of the NF-[Formula: see text]B signaling pathway during macrophage-mediated inflammatory responses.

scholarly journals Effect of Rosmarinic and Caffeic Acids on Inflammatory and Nociception Process in Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Giovana Duzzo Gamaro ◽  
Edna Suyenaga ◽  
Milene Borsoi ◽  
Joice Lermen ◽  
Patrícia Pereira ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
Rosmarinic Acid ◽  
Pleural Cavity ◽  
Biological Activities ◽  
Control Group ◽  
Tail Flick ◽  
Nociceptive Response ◽  
Tail Flick Latency ◽  
Balanced Distribution ◽  
Anti Inflammatory

Rosmarinic acid is commonly found in species of the Boraginaceae and the subfamily Nepetoideae (Lamiaceae). It has a number of interesting biological activities, for example, antiviral, antibacterial, anti-inflammatory, and antioxidant. The aim of the present study was to investigate the effect of the i.p. administration of caffeic and rosmarinic acid (5 and 10 mg/kg) on anti-inflammatory and nociceptive response using carrageenan-induced pleurisy model and tail-flick assay in rats. The analysis of cells in the pleural exudates revealed a reduction of 66% of the number of leukocytes that migrated to the pleural cavity in the animals treated with 5 mg/kg caffeic acid, and of 92.9% for the animals treated with 10 mg/kg in comparison with the control group. These exudates showed a balanced distribution of polymorphonuclear (PMN) and mononuclear (MN) cells, differently from the control group, in which PMN cells were predominant. The analysis to tail-flick latency was increased in the group treated with 10 mg/kg caffeic acid characterizing a nociceptive response. While there was no difference between control group and animals treated with rosmarinic.

scholarly journals Bridelia ferrugineaProduces Antineuroinflammatory Activity through Inhibition of Nuclear Factor-kappa B and p38 MAPK Signalling

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Olumayokun A. Olajide ◽  
Mutalib A. Aderogba ◽  
Uchechukwu P. Okorji ◽  
Bernd L. Fiebich
Keyword(s):  
P38 Mapk ◽  
Nuclear Translocation ◽  
Inos Protein ◽  
Bridelia Ferruginea ◽  
Mapk Signalling ◽  
Protein Expressions ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Inflammatory Action

Bridelia ferrugineais commonly used in traditional African medicine (TAM) for treating various inflammatory conditions. Extracts from the plant have been shown to exhibit anti-inflammatory property in a number ofin vivomodels. In this study the influence ofB. ferruginea(BFE) on the production of PGE2, nitrite, and proinflammatory cytokines from LPS-stimulated BV-2 microglia was investigated. The effects of BFE on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expressions were evaluated in LPS-activated rat primary microglia. The roles of NF-κB and MAPK signalling in the actions of BFE were also investigated. BFE (25–200 μg) inhibited the production of PGE2, nitrite, tumour necrosis factor-α(TNFα), and interleukin-6 (IL-6) as well as COX-2 and iNOS protein expressions in LPS-activated microglial cells. Further studies to elucidate the mechanism of anti-inflammatory action of BFE revealed interference with nuclear translocation of NF-κBp65 through mechanisms involving inhibition of IκB degradation. BFE prevented phosphorylation of p38, but not p42/44 or JNK MAPK. It is suggested thatBridelia ferrugineaproduces anti-inflammatory action through mechanisms involving p38 MAPK and NF-κB signalling.

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