scholarly journals Sec-O-glucosylhamaudol suppressed inflammatory reaction induced by LPS in RAW264.7 cells through inhibition of NF-κB and MAPKs signaling

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Guiming Liu ◽  
Jing Xie ◽  
Yurui Shi ◽  
Rongda Chen ◽  
Li Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bioactive Compound ◽  
Therapeutic Effects ◽  
Raw 264.7 ◽  
Pcr Assay ◽  
Raw 264.7 Cell ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Saposhnikovia Divaricata ◽  
Inflammation Cytokines

Abstract As a major bioactive compound from the Saposhnikovia divaricata (Turcz.) Schischk, sec-O-glucosylhamaudol (SOG), has been reported to have anti-nociceptive activity and high 5-lipoxygenase (5-LOX) activity. Nevertheless, the mechanism of the potential anti-inflammatory effects of SOG is unclear. The anti-inflammatory impacts of SOG in RAW 264.7 cell lines stimulated by LPS were explored in the present study. It was found that SOG dose-dependently reduced the emergence of inflammation cytokines, such as IL-6 and TNF-α in Raw264.7 murine macrophages stimulated by LPS. Real-time PCR assay demonstrated the SOG dose-dependently inhibited transcription of these cytokines as well. In addition, it was also found that NF-κB activation and MAPKs phosphorylation including p38, JNK and ERK1/2 induced by LPS were suppressed by SOG. Due to its anti-inflammatory activity, our results suggest that SOG might have therapeutic effects on inflammatory disease, such as acute lung injury or rheumatoid arthritis.

scholarly journals The Anti-Inflammatory Effect of KS23, A Novel Peptide Derived From Globular Adiponectin, on Endotoxin-Induced Uveitis in Rats

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Shi ◽  
Shaopin Zhu ◽  
Huiyi Jin ◽  
Junwei Fang ◽  
Xindan Xing ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Therapeutic Effects ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Globular Adiponectin ◽  
Anti Inflammatory

Purpose: Adiponectin has been shown to exert potent anti-inflammatory activities in a range of systemic inflammatory diseases. This study aimed to investigate the potential therapeutic effects of KS23, a globular adiponectin-derived peptide, on endotoxin-induced uveitis (EIU) in rats and lipopolysaccharide (LPS)-stimulated mouse macrophage-like RAW 264.7 cells.Methods: EIU was induced in Lewis rats by subcutaneous injection of LPS into a single footpad. KS23 or phosphate-buffered saline (PBS) was administered immediately after LPS induction via intravitreal injection. Twenty-four hours later, clinical and histopathological scores were evaluated, and the aqueous humor (AqH) was collected to determine the infiltrating cells, protein concentration, and levels of inflammatory cytokines. In vitro, cultured RAW 264.7 cells were stimulated with LPS in the presence or absence of KS23, inflammatory cytokine levels in the supernatant, nuclear translocation of nuclear factor kappa B (NF-κB) subunit p65, and the expression of NF-kB signaling pathway components were analyzed.Results: KS23 treatment significantly ameliorated the clinical and histopathological scores of EIU rats and reduced the levels of infiltration cells, protein, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the aqueous humor. Consistently, KS23 decreased the expression of TNF-α and IL-6 in the supernatant of LPS-stimulated RAW 264.7 cells and inhibited the LPS-induced nuclear translocation of NF-κB p65 and the phosphorylation of IKKα/β/IκBα/NF-κB.Conclusion: The in vivo and in vitro results demonstrated the anti-inflammatory effects of the peptide KS23 and suggested that KS23 is a compelling, novel therapeutic candidate for the treatment of ocular inflammation.

scholarly journals A New Flavonol From Saussurea involucrata With Anti-Inflammatory Activity

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110076
Author(s):  
Sheng Pan ◽  
Zi-Guan Zhu
Keyword(s):  
Nitric Oxide ◽  
Aerial Part ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Spectroscopic Methods ◽  
Soluble Extract ◽  
Saussurea Involucrata ◽  
Tnf Α ◽  
Anti Inflammatory

A new flavonol named 6-(2'',3''-epoxy-3''-methylbutyl)-resokaempferol (1), together with five known compounds (2-6) were isolated from the EtOAc-soluble extract of the aerial part of Saussurea involucrata. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for their anti-inflammatory effects by measuring the production of nitric oxide (NO) and TNF-α in vitro. Among them, compound 1 showed potential inhibitory activity on the production of NO and TNF-α in LPS-induced RAW 264.7 cells with IC50 values of 48.0 ± 1.5 and 41.4 ± 1.7 µM, respectively.

scholarly journals AB0043 EFFECT OF ANTI-INFLAMMATORY MEDICATION ON INTERACTION OF SYNOVIAL FIBROBLASTS WITH MACROPHAGES IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1054.1-1054
Author(s):  
M. Schmeller ◽  
M. Diller ◽  
R. Hasseli ◽  
A. Knothe ◽  
S. Rehart ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
Therapeutic Effects ◽  
Synergistic Activity ◽  
M1 Macrophages ◽  
Healthy Donors ◽  
Proinflammatory Activity ◽  
Anti Inflammatory

Background:One of the key mechanisms in the pathogenesis of rheumatoid arthritis (RA) is the interaction of macrophages and synovial fibroblasts during joint inflammation. Increased synergistic proinflammatory activity of both cell types leads to the release of high levels of proinflammatory cytokines, especially of interleukin-6 (IL-6), and of matrix degrading enzymes. If this mechanism is uncontrolled, progressive destruction of articular cartilage and bone will take place.In active disease, immediate anti-inflammatory treatment with glucocorticoids is usually replaced by disease-modifying anti-rheumatic drugs (DMARDS), especially by methotrexate (MTX) and biologics such as TNF-α- or IL-6-inhibitors. This led to great improvements in prognosis and outcome for RA patients. However, about 40% of patients experience no remission or suffer from side effects of medication. To optimize established substances and to develop new treatment strategies, it is necessary to understand the mechanisms underlying the limited therapeutic effects.Objectives:Evaluation of the effect of prednisolone, MTX, adalimumab, tocilizumab on IL-6 secretion by RA synovial fibroblasts (RASF) and macrophages.Methods:RA synovium was used for RASF isolation. Peripheral blood mononuclear cells (PBMCs) were isolated from blood of healthy donors and RA patients by using Ficoll© medium followed by density gradient centrifugation. Mononuclear cells were seeded on six well plates (6x10^6/well) and incubated for one week. Then they were stimulated with Interferon-у (20 ng/ml) and LPS (50 ng/ml) for 48h to initiate differentiation into proinflammatory M1 macrophages. The M1 macrophages were co-cultured with RASF (100.000/well) and different treatments added (prednisolone: 10, 25, 50, 75, 100 nM, 1 µM; adalimumab: 100, 500 µg/ml; tocilizumab: 1, 5 µg/ml; MTX: 0,5, 1, 5, 10, 100 nM, 1µM). After 24h culture supernatants were collected and IL-6- and TNFα-ELISAs were performed.Results:IL-6 concentrations of untreated controls were comparable, regardless whether M1 macrophages from healthy donors or RA-patients were used for co-culture. Prednisolone reduced co-culture-induced IL-6 up to 56% (p<0.001) in co-culture of RASF and M1 macrophages of healthy donors and up to 60% (p<0.001) in co-culture of RASF and RA M1 macrophages. Adalimumab reduced IL-6 up to 28% (p<0.05) in M1 of healthy donors and up to 45% (p<0.01) in RA M1 macrophage co-cultures. A minor reduction by 10-20% of IL-6 was observed with tocilizumab and no significant effect could be achieved after treatment with MTX.Conclusion:Prednisolone and adalimumab clearly decrease but do not eliminate proinflammatory synergistic activity of RASF and M1 macrophages. These results confirm the clinical observation, that there is a large number of RA-patients that independent of anti-inflammatory treatment still suffer from low-level joint inflammation.The synergistic proinflammatory activity of M1 macrophages and RASF seems to be a complex and multifactorial mechanism that is difficult to eliminate by a single treatment substance. Since it is one of the key mechanisms in RA pathogenesis, there is a critical need to investigate how therapy effects could be optimized. This study confirmed RASFs as one of the leading effector cells of increased synergistic proinflammatory activity, thus underlining their promising role as a treatment target in rheumatoid arthritis.Disclosure of Interests:None declared

scholarly journals Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 540-552 ◽  
Author(s):  
Hany H. Arab ◽  
Samir A. Salama ◽  
Tamer M. Abdelghany ◽  
Hany A. Omar ◽  
El-Shaimaa A. Arafa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mapk Pathway ◽  
Lipid Peroxide ◽  
Mitogen Activated Protein Kinase ◽  
Camel Milk ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.

scholarly journals Evaluation of Antioxidant, Anti-Inflammatory and Cytoprotective Properties of Ethanolic Mint Extracts from Algeria on 7-Ketocholesterol-Treated Murine RAW 264.7 Macrophages

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 184 ◽  
Author(s):  
Fatiha Brahmi ◽  
Thomas Nury ◽  
Meryam Debbabi ◽  
Samia Hadj-Ahmed ◽  
Amira Zarrouk ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Total Phenolic Content ◽  
Phenolic Content ◽  
Cytokine Secretion ◽  
Total Phenolic ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Raw 264.7 Macrophages ◽  
Tnf Α ◽  
Anti Inflammatory

The present study consisted in evaluating the antioxidant, anti-inflammatory and cytoprotective properties of ethanolic extracts from three mint species (Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L.) Huds (MR)) with biochemical methods on murine RAW 264.7 macrophages (a transformed macrophage cell line isolated from ascites of BALB/c mice infected by the Abelson leukemia virus). The total phenolic, flavonoid and carotenoid contents were determined with spectrophotometric methods. The antioxidant activities were quantified with the Kit Radicaux Libres (KRLTM), the ferric reducing antioxidant power (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The MS extract showed the highest total phenolic content, and the highest antioxidant capacity, while the MR extract showed the lowest total phenolic content and the lowest antioxidant capacity. The cytoprotective and anti-inflammatory activities of the extracts were quantified on murine RAW 264.7 macrophages treated with 7-ketocholesterol (7KC; 20 µg/mL: 50 µM) associated or not for 24 h and 48 h with ethanolic mint extracts used at different concentrations (25, 50, 100, 200 and 400 µg/mL). Under treatment with 7KC, an important inhibition of cell growth was revealed with the crystal violet test. This side effect was strongly attenuated in a dose dependent manner with the different ethanolic mint extracts, mainly at 48 h. The most important cytoprotective effect was observed with the MS extract. In addition, the effects of ethanolic mint extracts on cytokine secretion (Interleukin (IL)-6, IL-10, Monocyte Chemoattractant Protein (MCP)-1, Interferon (IFN)-ϒ, Tumor necrosis factor (TNF)-α) were determined at 24 h on lipopolysaccharide (LPS, 0.2 µg/mL)-, 7KC (20 µg/mL)- and (7KC + LPS)-treated RAW 264.7 cells. Complex effects of mint extracts were observed on cytokine secretion. However, comparatively to LPS-treated cells, all the extracts strongly reduce IL-6 secretion and two of them (MP and MR) also decrease MCP-1 and TNF-α secretion. However, no anti-inflammatory effects were observed on 7KC- and (7KC + LPS)-treated cells. Altogether, these data bring new evidences on the potential benefits (especially antioxidant and cytoprotective properties) of Algerian mint on human health.

scholarly journals Exogenous Heat Shock Cognate Protein 70 Suppresses LPS-Induced Inflammation by Down-Regulating NF-κB through MAPK and MMP-2/-9 Pathways in Macrophages

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2124 ◽  
Author(s):  
Erna Sulistyowati ◽  
Mei-Yueh Lee ◽  
Lin-Chi Wu ◽  
Jong-Hau Hsu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Critical Role ◽  
Matrix Metalloproteinase 2 ◽  
No Production ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Heat Shock Cognate Protein ◽  
Anti Inflammatory ◽  
Cognate Protein

Heat shock cognate protein 70 (HSC70), a molecular chaperone, is constitutively expressed by mammalian cells to regulate various cellular functions. It is associated with many diseases and is a potential therapeutic target. Although HSC70 also possesses an anti-inflammatory action, the mechanism of this action remains unclear. This current study aimed to assess the anti-inflammatory effects of HSC70 in murine macrophages RAW 264.7 exposed to lipopolysaccharides (LPS) and to explain its pathways. Mouse macrophages (RAW 264.7) in 0.1 µg/mL LPS incubation were pretreated with recombinant HSC70 (rHSC70) and different assays (Griess assay, enzyme-linked immune assay/ELISA, electrophoretic mobility shift assay/EMSA, gelatin zymography, and Western blotting) were performed to determine whether rHSC70 blocks pro-inflammatory mediators. The findings showed that rHSC70 attenuated the nitric oxide (NO) generation, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) expressions in LPS-stimulated RAW264.7 cells. In addition, rHSC70 preconditioning suppressed the activities and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9. Finally, rHSC70 diminished the nuclear translocation of nuclear factor-κB (NF-κB) and reduced the phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPK), and phosphatidylinositol-3-kinase (PI3K/Akt). We demonstrate that rHSC70 preconditioning exerts its anti-inflammatory effects through NO production constriction; TNF-α, and IL-6 suppression following down-regulation of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and MMP-2/MMP-9. Accordingly, it ameliorated the signal transduction of MAPKs, Akt/IκBα, and NF-κB pathways. Therefore, extracellular HSC70 plays a critical role in the innate immunity modulation and mechanisms of endogenous protective stimulation.

scholarly journals Asperuloside and Asperulosidic Acid Exert an Anti-Inflammatory Effect via Suppression of the NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages

2018 ◽  
Vol 19 (7) ◽  
pp. 2027 ◽  
Author(s):  
Jingyu He ◽  
Xianyuan Lu ◽  
Ting Wei ◽  
Yaqian Dong ◽  
Zheng Cai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways ◽  
Inflammatory Effect

Hedyotis diffusa is a folk herb that is used for treating inflammation-related diseases in Asia. Previous studies have found that iridoids in H. diffusa play an important role in its anti-inflammatory activity. This study aimed to investigate the anti-inflammatory effect and potential mechanism of five iridoids (asperuloside (ASP), asperulosidic acid (ASPA), desacetyl asperulosidic acid (DAA), scandoside methyl ester (SME), and E-6-O-p-coumaroyl scandoside methyl ester (CSME)) that are presented in H. diffusa using lipopolysaccharide (LPS)—induced RAW 264.7 cells. ASP and ASPA significantly decreased the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in parallel with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. ASP treatment suppressed the phosphorylation of the inhibitors of nuclear factor-kappaB alpha (IκB-α), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The inhibitory effect of ASPA was similar to that of ASP, except for p38 phosphorylation. In summary, the anti-inflammatory effects of ASP and ASPA are related to the inhibition of inflammatory cytokines and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, which provides scientific evidence for the potential application of H. diffusa.

scholarly journals A New Bithiophene from the Root of Echinops grijsii

2015 ◽  
Vol 10 (12) ◽  
pp. 1934578X1501001 ◽  
Author(s):  
Fang-Pin Chang ◽  
Chien-Chih Chen ◽  
Hui-Chi Huang ◽  
Sheng-Yang Wang ◽  
Jih-Jung Chen ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Cell Line ◽  
Natural Source ◽  
Inflammatory Activity ◽  
Raw 264.7 ◽  
Raw 264.7 Cell ◽  
Anti Inflammatory ◽  
First Time ◽  
Raw 264.7 Cell Line

A new bithiophene, 5-(4-hydroxy-3-methoxy-1-butyny)-2,2′-bithiophene (1), and sixteen known thiophenes: 2-(3,4-dihydroxybut-1-ynyl)-5-(penta-1,3-diynyl)thiophene (2), α-terthienyl (3), 5-(3,4-dihydroxybut-1-ynyl)-2,2′-bithiophene (4), 5-acetyl-2,2′-bithiophene (5), 5-formyl-2,2′-bithiophene (6), methyl 2,2′-bithiophene-5-carboxylate (7), 5-(but-3-en-1-ynyl)-2,2′-bithiophene (8), 5-(4-isovaleroyloxybut-1-ynyl)-2,2′-bithiophene (9), cardopatine (10), isocardopatine (11), 5-(3-hydroxy-4-isovaleroyloxybut-1-ynyl)-2,2′-bithiophene (12), 5-(3-hydroxymethyl-3-isovaleroyloxyprop-1-ynyl)-2,2′-bithiophene (13), 5-(4-hydroxy-1-butynyl)-2,2′-bithiophene (14), 5-(4-acetoxy-1-butynl)-2,2′-bithiophene (15), 2,2′-bithiophene-5-carboxylic acid (16) and 2-(4-hydroxybut-1-ynyl)-5-(penta-1,3-diynyl)thiophene (17) were isolated from the roots of Echinops grijisii Hance. Among them, compounds 6, 7 and 16 were isolated from a natural source for the first time. Compounds 2, 4 and 14 exhibited significant anti-inflammatory activity against nitrite of LPS-stimulated production in the RAW 264.7 cell line.

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