Dose-Dependent Anti-inflammatory Effect of Inhaled Mometasone Furoate/Formoterol in Subjects With Asthma and High Baseline Exhaled Nitric Oxide and Sputum Eosinophils

Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.

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Selective iNOS Inhibition Attenuates Acetylcholine- and Bradykinin-induced Vasoconstriction in Lipopolysaccharide-exposed Rat Lungs

Anesthesiology ◽

10.1097/00000542-199912000-00026 ◽

1999 ◽

Vol 91 (6) ◽

pp. 1724-1724 ◽

Cited By ~ 33

Author(s):

Lars G. Fischer ◽

Damian J. Horstman ◽

Klaus Hahnenkamp ◽

Nancy E. Kechner ◽

George F. Rich

Keyword(s):

Nitric Oxide ◽

Exhaled Nitric Oxide ◽

Control Group ◽

Biochemical Engineering ◽

Inos Inhibitor ◽

Nos Inhibitor ◽

Inos Inhibitors ◽

Oxide Synthase ◽

Inos Inhibition ◽

Dose Dependent

Background Nonselective nitric oxide synthase (NOS) inhibition has detrimental effects in sepsis because of inhibition of the physiologically important endothelial NOS (eNOS). The authors hypothesized that selective inducible NOS (iNOS) inhibition would maintain eNOS vasodilation but prevent acetylcholine- and bradykinin-mediated vasoconstriction caused by lipopolysaccharide-induced endothelial dysfunction. Methods Rats were administered intraperitoneal lipopolysaccharide (15 mg/kg) with and without the selective iNOS inhibitors L-N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg), dexamethasone (1 mg/kg), or the nonselective NOS inhibitor Nomega-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Six hours later, the lungs were isolated and pulmonary vasoreactivity was assessed with hypoxic vasoconstrictions (3% O2), acetylcholine (1 microg), Biochemical Engineering, and bradykinin (3 microg). In additional lipopolysaccharide experiments, L-NIL (10 microM) or 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 100 microM), a selective muscarinic M3 antagonist, was added into the perfusate. Results Exhaled nitric oxide was higher in the lipopolysaccharide group (37.7+/-17.8 ppb) compared with the control group (0.4+/-0.7 ppb). L-NIL and dexamethasone decreased exhaled nitric oxide in lipopolysaccharide rats by 83 and 79%, respectively, whereas L-NAME had no effect. In control lungs, L-NAME significantly decreased acetylcholine- and bradykinin-induced vasodilation by 75% and increased hypoxic vasoconstrictions, whereas L-NIL and dexamethasone had no effect. In lipopolysaccharide lungs, acetylcholine and bradykinin both transiently increased the pulmonary artery pressure by 8.4+/-2.0 mmHg and 35.3+/-11.7 mmHg, respectively, immediately after vasodilation. L-NIL and dexamethasone both attenuated this vasoconstriction by 70%, whereas L-NAME did not. The acetylcholine vasoconstriction was dose-dependent (0.01-1.0 microg), unaffected by L-NIL added to the perfusate, and abolished by 4-DAMP. Conclusions In isolated perfused lungs, acetylcholine and bradykinin caused vasoconstriction in lipopolysaccharide-treated rats. This vasoconstriction was attenuated by administration of the iNOS inhibitor L-NIL but not with L-NAME. Furthermore, L-NIL administered with lipopolysaccharide preserved endothelium nitric oxide-dependent vasodilation, whereas L-NAME did not.

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Carbon Monoxide-Neuroglobin Axis Targeting Metabolism Against Neuroinflammation

10.21203/rs.3.rs-852619/v1 ◽

2021 ◽

Author(s):

Daniela Dias-Pedroso ◽

José S. Ramalho ◽

Vilma A. Sardão ◽

John G. Jones ◽

Carlos C. Romão ◽

...

Keyword(s):

Nitric Oxide ◽

Carbon Monoxide ◽

Oxygen Consumption ◽

Inflammatory Response ◽

Microglial Cell ◽

Cell Metabolism ◽

Competent Cell ◽

Metabolic Shift ◽

Anti Inflammatory ◽

Inflammatory Effect

Abstract Microglia are the immune competent cell of the central nervous system (CNS), promoting brain homeostasis and regulating inflammatory response against infection and injury. Chronic or exacerbated neuroinflammation is a cause of damage in several brain pathologies. Endogenous carbon monoxide (CO), produced from the degradation of heme, is described as anti-apoptotic and anti-inflammatory in several contexts, including in the CNS. Neuroglobin (Ngb) is a haemoglobin-homologous protein, which upregulation triggers antioxidant defence and prevents neuronal apoptosis. Thus, we hypothesized a crosstalk between CO and Ngb, in particular, that the anti-neuroinflammatory role of CO in microglia depends on Ngb. A novel CO-releasing molecule (ALF826) based on molybdenum was used for delivering CO in microglial culture.BV-2 mouse microglial cell line was challenged with lipopolysaccharide (LPS) for triggering inflammation, and after 6h ALF826 was added. CO exposure limited inflammation by decreasing inducible nitric oxide synthase (iNOS) expression and the production of nitric oxide (NO) and tumour necrosis factor-a (TNF-a), and by increasing interleukine-10 (IL-10) release. CO-induced Ngb upregulation correlated in time with CO’s anti-inflammatory effect. Moreover, knocking down Ngb reversed the anti-inflammatory effect of CO, suggesting that dependents on Ngb expression. CO-induced Ngb upregulation was independent on ROS signalling, but partially dependent on the transcriptional factor SP1. Finally, microglial cell metabolism is also involved in the inflammatory response. In fact, LPS treatment decreased oxygen consumption in microglia, indicating a switch to glycolysis, which is associated with a proinflammatory. While CO treatment increased oxygen consumption, reverting LPS effect and indicating a metabolic shift into a more oxidative metabolism. Moreover, in the absence of Ngb this phenotype was no longer observed, indicating Ngb is needed for CO’s modulation of microglial metabolism. Finally, the metabolic shift induced by CO did not depend on alteration of mitochondrial population. In conclusion, neuroglobin emerges for the first time as a key player for CO signalling against exacerbated neuroinflammation in microglia.

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Effects of esculentoside A on turnour necrosis factor production by mice peritoneal macrophages

Mediators of Inflammation ◽

10.1155/s0962935192000565 ◽

1992 ◽

Vol 1 (6) ◽

pp. 375-377 ◽

Cited By ~ 5

Author(s):

Fang Jun ◽

Zheng Qin Yue ◽

Wang Hong Bin ◽

Ju Dian Wen ◽

Yi Yang Hua

Keyword(s):

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Inflammatory Mediator ◽

Platelet Activating Factor ◽

Peritoneal Macrophages ◽

Dependent Manner ◽

Anti Inflammatory ◽

Dose Dependent ◽

Necrosis Factor ◽

Inflammatory Effect

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments showed that it had strong anti-inflammatory effects. Tumour necrosis factor (TNF) is an important inflammatory mediator. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF production from macrophages was altered by EsA under lipopolysaccharide (LPS) stimulated conditions. EsA was found to decrease both extracellular and cell associated TNF production in a dose dependent manner at concentrations higher than 1 μmol/l EsA. Previous studies have showed that EsA reduced the releasing of platelet activating factor (PAF) from rat macrophages. The reducing effects of EsA on the release of TNF and PAF may explain its anti-inflammatory effect.

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Inhibition of neutrophil L-selectin shedding: a potential anti-inflammatory effect of aprotinin

Perfusion ◽

10.1177/026765910001500604 ◽

2000 ◽

Vol 15 (6) ◽

pp. 495-499 ◽

Cited By ~ 15

Author(s):

George Asimakopoulos ◽

Kenneth M Taylor ◽

Dorian O Haskard ◽

R Clive Landis

Keyword(s):

Endothelial Cell ◽

Venous Blood ◽

Platelet Activating Factor ◽

Surface Expression ◽

Cell Interaction ◽

Dose Dependent Fashion ◽

Anti Inflammatory ◽

Dose Dependent ◽

Inflammatory Action ◽

Inflammatory Effect

The cardiopulmonary bypass (CPB)-related inflammatory response involves leucocyte activation and increased leucocyte-endothelial cell interaction. L-selectin is an adhesion molecule expressed on the surface of leucocytes which participates in the initial rolling step of the leucocyte-endothelial cell adhesion cascade. L-selectin is proteolytically cleaved off the surface of leucocytes when they become activated, an event that is regarded as a marker of leucocyte activation. Aprotinin is a protease inhibitor that has been used in cardiac surgery as a haemostatic agent and also exhibits certain anti-inflammatory properties. In this study, peripheral venous blood from volunteers was pre-incubated with aprotinin at 200, 800 and 1600 kallikrein inhibiting units (kiu)/ml and stimulated with the chemoattractants N-formyl-methyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF). Surface expression of L-selectin on neutrophils was measured using a monoclonal antibody and flow cytometry. The results demonstrate that aprotinin inhibits shedding of L-selectin in a dose-dependent fashion ( p=0.0278 and 0.0005, respectively, at 800 and 1600 kiu/ml for fMLP-stimulated shedding; p=0.0017 and 0.0010, respectively, at 200 and 800 kiu/ml for PAF-stimulated shedding). This effect may be of significance with respect to the anti-inflammatory action of aprotinin in patients undergoing CPB.

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Anti-Inflammatory Activity of Extract Mixture of Annona senegalensis Pers. and Piliostigma thonningii (Schum.)

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i6-s.4605 ◽

2020 ◽

Vol 10 (6-s) ◽

pp. 103-108

Author(s):

Komlatsè Togbenou ◽

Kokou Idoh ◽

Kossivi Dosseh ◽

Tchazou Kpatcha ◽

Amégnona Agbonon

Keyword(s):

Nitric Oxide ◽

Ethanolic Extract ◽

No Production ◽

Leukocyte Infiltration ◽

Inflammation Markers ◽

Asthma Model ◽

Piliostigma Thonningii ◽

Anti Inflammatory ◽

Inflammatory Component ◽

Inflammatory Effect

Introduction: Annona senegalensis Pers (Annonaceae) and Piliostigma thonningii (Schum.) (Leguminoseae) are two medicinal plants used, often in combination, in traditional Togolese medicine for the treatment of diseases with an inflammatory component. Objective: The aim of this study is to evaluate the anti-inflammatory effect of the hydro-ethanolic extract (EHEM) of the combination of A. senegalensis and P. thonningii (1: 1, m: m). Methods: The ovalbumin-induced allergic airway asthma model was used. Animals made asthmatic were treated with EHEM at doses of 250 and 500 mg / kg. Inflammation markers including histamine, nitric oxide (NO), vascular leakage, leukocyte infiltration in the airways, and malondialdehyde (MDA), were measured. Results: Compared to the SNT group, EHEM inhibits the infiltration of the airways by leukocytes (850,00 × 103 ± 50 cells / mL vs 1830 × 103 ± 53,85 cells / mL for ST500 mg / kg, P <0,05). It inhibited vascular permeability to Evans Blue (10,40 ± 0,270 μg / mL vs ST500, p<0,05). It inhibited histamine release (13,95 ± 0,937 μg / mL vs 32,78 ± 1,044 μg / mL, p<0,05) and NO production (0,211 ± 0,008 Μm vs 0,315 ± 0,022 μM, p<0,05). It finally inhibited MDA production (14,66 ± 0,533 nM / mL vs 9,014 ± 0,366 nM / mL and 7,149 ± 0,300 nM / mL, p<0,05) in lung tissue. Conclusion: Our results suggest that EHEM inhibits OVA-induced inflammation. These results justify the use of this combination of plants in traditional Togolese medicine. Keywords: Inflammation, malondialdehyde, Annona senegalensis, Piliostigma thonningii.

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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

International Journal of Molecular Sciences ◽

10.3390/ijms19072027 ◽

2018 ◽

Vol 19 (7) ◽

pp. 2027 ◽

Cited By ~ 18

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.

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Anti-inflammatory effect and inhibition of nitric oxide production by targeting COXs and iNOS enzymes with the 1,2-diphenylbenzimidazole pharmacophore

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2020.115427 ◽

2020 ◽

Vol 28 (9) ◽

pp. 115427

Author(s):

Mónica I. García-Aranda ◽

Jazmin E. Gonzalez-Padilla ◽

Carlos Z. Gómez-Castro ◽

Yolanda M. Gómez-Gómez ◽

Martha C. Rosales-Hernández ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Production ◽

Oxide Production ◽

Anti Inflammatory ◽

Inflammatory Effect

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Anti-inflammatory Effect of Pratol in LPS-stimulated RAW 264.7 Cells via NF-κB Signaling Pathways

Natural Product Communications ◽

10.1177/1934578x1801300509 ◽

2018 ◽

Vol 13 (5) ◽

pp. 1934578X1801300

Author(s):

You Chul Chung ◽

Sung-Min Park ◽

Jin Hwa Kim ◽

Geun Soo Lee ◽

Jung No Lee ◽

...

Keyword(s):

Nitric Oxide ◽

Trifolium Pratense ◽

Skin Diseases ◽

Inflammatory Diseases ◽

Red Clover ◽

Raw 264.7 Cells ◽

Prostaglandin E ◽

Raw 264.7 ◽

Anti Inflammatory ◽

Inflammatory Effect

The Trifolium pratense L. (red clover), which blossoms, leaves and stems can be used as medicines for treatment of burns, skin diseases, diabetes and other diseases. Recently study shown that pratol (7-hydroxy-4-methoxyflavone), an O-methylated flavone in T. pratense has been evaluated to induce melanogenesis in B16F10 melanoma cells. However, the anti-inflammatory effect of pratol has not been reported. In this study, we investigated the effects of pratol on anti-inflammation. We also studied the mechanism of action of pratol in LPS-stimulated RAW 264.7 cells. The cells were treated with various concentration of pratol (25, 50, or 100 μM) and 25 μM ammonium pyrrolidinedithiocarbamate (APDC) was used as control. The results in LPS-stimulated RAW 264.7 cells showed that pratol significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without any cytotoxic. In addition, pratol strongly decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooygenase (COX-2). Furthermore, pratol reduced proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. We also found that pratol strongly inhibited activation of nuclear factor kappa B (NF-κB) by reducing the p65 phosphorylation and protecting inhibitory factor kappa B alpha (IκBα) degradation. The results suggest that, pratol may be used to treat or prevent inflammatory diseases such as dermatitis, arthritis, cardiovascular and cancer.

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