scholarly journals Mechanisms of TQ-6, a Novel Ruthenium-Derivative Compound, against Lipopolysaccharide-Induced In Vitro Macrophage Activation and Liver Injury in Experimental Mice: The Crucial Role of p38 MAPK and NF-κB Signaling

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 217 ◽  
Author(s):  
Chih-Hsuan Hsia ◽  
Marappan Velusamy ◽  
Thanasekaran Jayakumar ◽  
Yen-Jen Chen ◽  
Chih-Wei Hsia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
P38 Mapk ◽  
Macrophage Activation ◽  
Molecular Mechanisms ◽  
No Production ◽  
Dependent Manner ◽  
Tnf Α ◽  
Anti Inflammatory

Several studies have reported that metal complexes exhibit anti-inflammatory activities; however, the molecular mechanism is not well understood. In this study, we used a potent ruthenium (II)-derived compound, [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), to investigate the molecular mechanisms underlying the anti-inflammatory effects against lipopolysaccharide (LPS)-induced macrophage activation and liver injury in mice. Treating LPS-stimulated RAW 264.7 cells with TQ-6 suppressed nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner. The LPS-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) were reduced in TQ-6-treated cells. TQ-6 suppressed, LPS-stimulated p38 MAPK phosphorylation, IκBα degradation, and p65 nuclear translocation in cells. Consistent with the in vitro studies, TQ-6 also suppressed the expression of iNOS, TNF-α, and p65 in the mouse model with acute liver injury induced by LPS. The present study showed that TQ-6 could protect against LPS-induced in vitro inflammation in macrophage and in vivo liver injury in mice, and suggested that NF-κB could be a promising target for protecting against LPS-induced inflammation and liver injury by TQ-6. Therefore, TQ-6 can be a potential therapeutic agent for treating inflammatory diseases.

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF TINOCRISPOSIDE BY INHIBITING NITRIC OXIDE PRODUCTION IN LIPOPOLYSACCHARIDES-STIMULATED RAW 264.7 CELLS

2018 ◽  
Vol 11 (4) ◽  
pp. 149 ◽  
Author(s):  
Adek Zamrud Adnan ◽  
Muhammad Taher ◽  
Tika Afriani ◽  
Annisa Fauzana ◽  
Dewi Imelda Roesma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Positive Control ◽  
Inflammatory Activity ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory

 Objective: The aim of this study was to investigate in vitro anti-inflammatory activity of tinocrisposide using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophage cells. Tinocrisposide is a furano diterpene glycoside that was isolated in our previous study from Tinospora crispa.Methods: Anti-inflammatory effect was quantified spectrometrically using Griess method by measuring nitric oxide (NO) production after the addition of Griess reagent.Results: The sample concentrations of 1, 5, 25, 50, and 100 μM and 100 μM of dexamethasone (positive control) have been tested against the LPS-stimulated RAW 264.7 cells, and the results showed NO level production of 39.23, 34.00, 28.9, 20.25, 16.3, and 13.68 μM, respectively, and the inhibition level of 22.67, 33.00, 43.03, 60.10, 68.00, and 73%, respectively.Conclusions: From the study, it could be concluded that tinocrisposide was able to inhibit the formation of NO in the LPS-stimulated RAW 264.7 cells in concentration activity-dependent manner, with half-maximal inhibition concentration 46.92 μM. It can be developed as anti-inflammatory candidate drug because NO is a reactive nitrogen species which is produced by NO synthase. The production of NO has been established as a mediator in inflammatory diseases.

Anti-inflammatory Activity of Herbal Medicines: Inhibition of Nitric Oxide Production and Tumor Necrosis Factor-α Secretion in an Activated Macrophage-like Cell Line

2005 ◽  
Vol 33 (03) ◽  
pp. 415-424 ◽  
Author(s):  
Eunkyue Park ◽  
Susan Kum ◽  
Chuanhua Wang ◽  
Seung Yong Park ◽  
Bo Sook Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis ◽  
No Production ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Tnf Α ◽  
Activated Macrophage ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor

Houttuynia cordata Thunb. (HC), Glycyrrhiza uralensis Fischer (GU), Forsythia suspense (Thunb.) Vahl (FS), and Lonicera japonica Thunb. (LJ) are Chinese herbs known to possess anti-inflammatory properties. The effects of aqueous extracts of these herbs on the production of the pro-inflammatory mediators, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were examined in an activated macrophage-like cell line, RAW 264.7 cells. Aqueous extracts from FS at 0.0625–2.0 mg/ml inhibited in vitro production of NO and secretion of TNF-α in a dose-dependent manner. FS at 1.0–2.0 mg/ml and 0.125–2.0 mg/ml significantly inhibited NO production and TNF-α, respectively. An extract of LJ demonstrated potent inhibition of both NO production and TNF-α secretion in a dose-dependent manner. An aqueous extract from HC inhibited NO production in a dose-dependent manner, but minimally (approximately 30%) inhibited TNF-α secretion at 0.0625 and 0.125 mg/ml. In contrast, an aqueous extract of GU had a minimal effect on both the production of NO and the secretion of TNF-α. Viability of cells at all concentrations studied was unaffected as determined by MTT cytotoxicity assay and trypan blue dye exclusion. These results suggest that aqueous extracts from FS, LJ and HC have anti-inflammatory actions as measured by inhibition of NO production and/or TNF-α secretion.

Moringa Fruit Inhibits LPS-Induced NO/iNOS Expression through Suppressing the NF-κB Activation in RAW264.7 Cells

2013 ◽  
Vol 41 (05) ◽  
pp. 1109-1123 ◽  
Author(s):  
Hyo-Jin Lee ◽  
Yun-Jeong Jeong ◽  
Tae-Sung Lee ◽  
Yoon-Yub Park ◽  
Whi-Gun Chae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Biologically Active ◽  
Raw264.7 Cells ◽  
No Production ◽  
Dependent Manner ◽  
Fruit Extract ◽  
Tnf Α ◽  
Anti Inflammatory

In this study, we evaluated the anti-inflammatory effects of moringa (Moringa oleifera Lam.), a natural biologically active substance, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. The moringa fruit extract most effectively inhibited LPS-induced NO production and levels of inducible nitric oxide synthase (iNOS). The moringa fruit extract also was shown to suppress the production of inflammatory cytokines including IL-1β, TNF-α, and IL-6. Furthermore, moringa fruit extract inhibited the cytoplasmic degradation of I κ B -α and the nuclear translocation of p65 proteins, resulting in lower levels of NF -κ B transactivation. Collectively, the results of this study demonstrate that moringa fruit extract reduces the levels of pro-inflammatory mediators including NO , IL-1β, TNF-α, and IL-6 via the inhibition of NF -κ B activation in RAW264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of moringa fruit extract.

scholarly journals Leukotriene B4 Induces Nitric Oxide Synthesis in Trypanosoma cruzi-Infected Murine Macrophages and Mediates Resistance to Infection

2002 ◽  
Vol 70 (8) ◽  
pp. 4247-4253 ◽  
Author(s):  
A. Talvani ◽  
F. S. Machado ◽  
G. C. Santana ◽  
A. Klein ◽  
L. Barcelos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Trypanosoma Cruzi ◽  
Leukotriene B4 ◽  
No Production ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The production of nitric oxide (NO) by gamma interferon (IFN-γ)-activated macrophages is a major effector mechanism during experimental Trypanosoma cruzi infection. In addition to IFN-γ, chemoattractant molecules, such as platelet-activating factor (PAF) and CC chemokines, may also activate macrophages to induce NO and mediate the killing of T. cruzi in an NO-dependent manner. Here we investigated the ability of leukotriene B4 (LTB4) to induce the production of NO by macrophages infected with T. cruzi in vitro and whether NO mediated LTB4-induced parasite killing. The activation of T. cruzi-infected but not naive murine peritoneal macrophages with LTB4 induced the time- and concentration-dependent production of NO. In addition, low concentrations of LTB4 acted in synergy with IFN-γ to induce NO production. The NO produced mediated LTB4-induced microbicidal activity in macrophages, as demonstrated by the inhibitory effects of an inducible NO synthase inhibitor. LTB4-induced NO production and parasite killing were LTB4 receptor dependent and were partially blocked by a PAF receptor antagonist. LTB4 also induced significant tumor necrosis factor alpha (TNF-α) production, and blockade of TNF-α suppressed LTB4-induced NO release and parasite killing. A blockade of LTB4 or PAF receptors partially inhibited IFN-γ-induced NO and TNF-α production but not parasite killing. Finally, daily treatment of infected mice with CP-105,696 was accompanied by a significantly higher level of blood parasitemia, but not lethality, than that seen in vehicle-treated animals. In conclusion, our results suggest a role for LTB4 during experimental T. cruzi infection. Chemoattractant molecules such as LTB4 not only may play a major role in leukocyte migration into sites of inflammation in vivo but also, in the event of an infection, may play a relevant role in the activation of recruited leukocytes to kill the invading microorganism in an NO-dependent manner.

In Vitro and in Vivo Therapeutics of β-Thujaplicin on Lps-Induced Inflammation in Macrophages and Septic Shock in Mice

2012 ◽  
Vol 25 (1) ◽  
pp. 39-48 ◽  
Author(s):  
M-F. Shih ◽  
L-Y. Chen ◽  
P-J. Tsai ◽  
J-Y. Cherng
Keyword(s):  
Septic Shock ◽  
Mortality Rate ◽  
Molecular Mechanisms ◽  
No Production ◽  
Active Constituent ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

β-thujaplicin, an active constituent from Chamaecyparis obtusa, has been shown to have acaricidal and antimicrobial effects. Very few studies have focused on the potential of the anti-inflammatory effect of β-thujaplicin. Moreover, its capability of inhibiting inflammatory mediators e.g. TNF-α gene transcription, nitric oxide (NO) and prostaglandin E2, remains unknown. Besides those molecular mechanisms behind the anti-inflammatory effect of β-thujaplicin, solid proof of its effectiveness in vivo has not yet been studied. In our study, in vitro effects of β-thujaplicin were verified on RAW 264.7 macrophages which were stimulated by LPS. Indomethacin was used as a positive control. The inducible NO production after stimulation was measured by Griess reagent. PGE2, IL-6 and TNF-α were measured by ELISA methods. Protein expressions of iNOS, COX2, and NF-κB were evaluated by Western blotting. Septic ICR mice were administered 20 mg/kg of LPS and then the mortality rate was monitored. Within the concentration range which was devoid of cytotoxicty, β-thujaplicin exhibited a clear dose-dependent inhibition on LPS-induced NO production. Furthermore, β-thujaplicin inhibited LPS-induced PGE2, IL-6, and TNF-α production as well as iNOS, COX2, and NF-κB protein expression more substantially potent than indomethacin. In agreement with the in vitro study, β-thujaplicin was shown to be effective in vivo for inhibiting LPS-induced NO and TNF-α production and a significant decrease in mortality rate of mice suffering from septic shock was observed. This study demonstrates the potential of β-thujaplicin in treatment of inflammation and sepsis. These effects occur through an efficient blockage of TNF-α and iNOS production, β-thujaplicin efficacy is comparable to that of indomethacin thus it can be a substitution but bear less depletion of PGE2, making this compound very promising in clinical applications.

scholarly journals Antioxidant and Anti-Inflammatory Effects of Korean Black Ginseng Extract through ER Stress Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 62
Author(s):  
Mi-Yeong An ◽  
So Rok Lee ◽  
Hye-Jeong Hwang ◽  
Ju-Gyeong Yoon ◽  
Hae-Jeung Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Er Stress ◽  
Immune Cell ◽  
Antioxidant Effect ◽  
No Production ◽  
Dependent Manner ◽  
Black Ginseng ◽  
Anti Inflammatory

The excessive release of reactive oxygen species (ROS) can result in the development of chronic inflammation. The mechanisms involved in inflammation are various, with endoplasmic reticulum (ER) stress known to be among them. We have previously shown that black ginseng (BG) reduced lipid accumulation in and enhanced the antioxidant function of the liver in vitro and in vivo mostly due to ginsenoside Rb1, Rg3 and Rk1 components. Therefore, this study investigated the antioxidant effect of BG on the intestines and its possible mechanistic pathway through ER stress. The results showed that BG extract decreased ROS and nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression levels in vitro, and these results were confirmed by zebrafish embryos in vivo. However, this phenotype was abolished in the absence of inositol-requiring enzyme 1 (IRE1α) but not in the absence of protein kinase RNA (PKR)-like ER-resistant kinase (PERK) or X-box-binding protein 1 (XBP1) in the mouse embryo fibroblast (MEF) knockout (KO) cells, suggesting that BG elicits an antioxidant effect in an IRE1α-dependent manner. Antioxidant and anti-inflammatory effects were assessed in the liver and intestines of the mouse model affected by nonalcoholic fatty liver disease (NAFLD), which was induced by a high-fat/high-fructose diet. In the liver, BG treatment rescued NAFLD-induced glutathione (GSH), catalase (CAT), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 expression. In the intestines, BG also rescued NAFLD-induced shortened villi, inflammatory immune cell infiltration, upregulated IL-6, cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding homologous protein (CHOP) and binding immunoglobulin protein (BiP) expression. In conclusion, our results show that BG reduces ROS and NO production followed by inflammation in an IRE1α-dependent and XBP1-independent manner. The results suggest that BG provides antioxidant and anti-inflammatory effects through an ER stress mechanism.

scholarly journals Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1545
Author(s):  
Hwa-Young Song ◽  
Da-Eun Jeong ◽  
Mina Lee
Keyword(s):  
Biological Activities ◽  
Radical Scavenging ◽  
No Production ◽  
Dependent Manner ◽  
Optimal Method ◽  
Concentration Dependent Manner ◽  
Osmanthus Fragrans ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Extracellular Regulated Kinase

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

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 Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

2017 ◽  
Vol 43 (5) ◽  
pp. 2074-2087 ◽  
Author(s):  
Liling Yang ◽  
Xiangjun Zhou ◽  
Weijuan Huang ◽  
Qin Fang ◽  
Jianlan Hu ◽  
...  
Keyword(s):  
Signalling Pathway ◽  
Dependent Manner ◽  
Zebrafish Model ◽  
Lps Challenge ◽  
Cell Counts ◽  
Tnf Α ◽  
Forsythia Suspensa ◽  
Anti Inflammatory

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

scholarly journals Anti-inflammatory and Matrix Metallopeptidase-1-Inhibitory Effects of the Cassia obtusifolia L. Seed Extract on Particulate Matter-induced Skin

2021 ◽  
Vol 19 (3) ◽  
pp. 355-363
Author(s):  
Jung-Wook Kang ◽  
In-Chul Lee
Keyword(s):  
Particulate Matter ◽  
Seed Extract ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Cassia Obtusifolia ◽  
Tnf Α ◽  
Matrix Metallopeptidase ◽  
Anti Inflammatory

Purpose: This study aimed to investigate the effects of the Cassia obtusifolia L. seed extract (CSE) on particulate matter (PM)-induced skin.Methods: The effects of CSE on cell viability were evaluated using a skin cell line. To determine the anti-inflammatory effects and matrix metallopeptidase-1 (MMP-1)-inhibitory effects of CSE on PM-induced skin, NO and MMP-1 expressions were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the effects of CSE was investigated the induction of IL-8 and TNF-α treated PM on reconstructed human full thickness skin models.Results: It was observed that CSE decreased NO production in PM-induced RAW 264.7 cells without cytotoxicity. In addition, CSE decreased the expression of MMP-1 in PM-induced cells in a dose-dependent manner. CSE decreased IL-8 and TNF-α production in a PM-reconstructed human skin model.Conclusion: These results indicate that CSE could be used as a cosmetic material to induce anti-inflammation and inhibition of MMP-1 in PM-induced skin.

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