scholarly journals Sudachinoid- and Ichangensin-Type Limonoids from Citrus junos Downregulate Pro-Inflammatory Cytokines

2020 ◽  
Vol 21 (18) ◽  
pp. 6963
Author(s):  
Jihun Shin ◽  
Hwa Young Song ◽  
Mina Lee
Keyword(s):  
Inflammatory Cytokines ◽  
Human Colon ◽  
Dominant Group ◽  
Citrus Junos ◽  
Mouse Macrophages ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.

scholarly journals ANTI-INFLAMMATORY EFFECT OF ELETTARIA CARDAMOM OIL ON CARRAGEENAN-INDUCED PAW EDEMA USING RATS BASED ON TUMOR NECROSIS FACTOR α, INTERLEUKIN 6, AND INTERLEUKIN 1 LEVELS IN SERUM

2018 ◽  
Vol 11 (2) ◽  
pp. 207 ◽  
Author(s):  
Nithya Sermugapandian ◽  
Rubini R ◽  
Martina V
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Paw Edema ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

 Objective: In this study, we evaluated the anti-inflammatory effect of Elettaria cardamom oil and the underlying mechanism using in vivo models of inflammation.Methods: Male Sprague–Dawley rats, 4-6 weeks old, weighing 120-130 gms are used for the study. The anti-inflammatory study of E. cardamom oil was studied by injecting 0.1 ml of 1% carrageenan to the subplantar region of the right hind paw of rats. The development of acute inflammation was measured at the end of every 1st, 2nd, 3rd, 4th, 5th, and 6th h using plethysmometer.Results: As results from the above study, E. cardamom oil at a dose of 0.175 ml/kg was less significant than that of E. cardamom oil at a dose of 0.280 ml/kg when given orally. A p<0.05 shows a significant decrease in paw edema. It also reduced the levels of pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL) 1, and IL 6 levels in the serum. The histopathology results also showed a significant reduction of congested blood vessels with no marked impression for inflammation.Conclusion: E. cardamom oil possesses anti-inflammatory activity in dose-dependent manner as they inhibit the levels of pro-inflammatory cytokines.

scholarly journals Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon

2017 ◽  
Vol 131 (21) ◽  
pp. 2611-2626 ◽  
Author(s):  
Daniel G. Couch ◽  
Chris Tasker ◽  
Elena Theophilidou ◽  
Jonathan N. Lund ◽  
Saoirse E. O’Sullivan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Human Colon ◽  
Interferon Γ ◽  
Cytokine Levels ◽  
Drug Treatments ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Trpv1 Antagonist ◽  
Factor Α

Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Design: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55. Results: IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti-inflammatory in IBD and appendicitis explants. Conclusion: PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy.

scholarly journals Antidepressant-Like Effect and Mechanism of Action of Honokiol on the Mouse Lipopolysaccharide (LPS) Depression Model

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2035 ◽  
Author(s):  
Bo Zhang ◽  
Ping-Ping Wang ◽  
Kai-Li Hu ◽  
Li-Na Li ◽  
Xue Yu ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Mechanism Of Action ◽  
Tail Suspension Test ◽  
Interferon Γ ◽  
Biologically Active ◽  
Free Calcium ◽  
Immobility Time ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.

scholarly journals Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages

2017 ◽  
Vol 474 (4) ◽  
pp. 521-537 ◽  
Author(s):  
Nicola J. Darling ◽  
Rachel Toth ◽  
J. Simon C. Arthur ◽  
Kristopher Clark
Keyword(s):  
Inflammatory Cytokines ◽  
Drug Targets ◽  
Macrophage Polarization ◽  
Macrophage Phenotype ◽  
Integral Role ◽  
Inflammatory Phenotype ◽  
Low Levels ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Pharmacological inhibition of the SIKs induces a macrophage phenotype characterized by the secretion of high levels of anti-inflammatory cytokines, including interleukin (IL)-10, and the secretion of very low levels of pro-inflammatory cytokines, such as tumour necrosis factor α. The SIKs, therefore, represent attractive new drug targets for the treatment of macrophage-driven diseases, but which of the three isoforms, SIK1, SIK2 or SIK3, would be appropriate to target remains unknown. To address this question, we developed knock-in (KI) mice for SIK1, SIK2 and SIK3, in which we introduced a mutation that renders the enzymes catalytically inactive. Characterization of primary macrophages from the single and double KI mice established that all three SIK isoforms, and in particular SIK2 and SIK3, contribute to macrophage polarization. Moreover, we discovered that inhibition of SIK2 and SIK3 during macrophage differentiation greatly enhanced the production of IL-10 compared with their inhibition in mature macrophages. Interestingly, macrophages differentiated in the presence of SIK inhibitors, MRT199665 and HG-9-91-01, still produced very large amounts of IL-10, but very low levels of pro-inflammatory cytokines, even after the SIKs had been reactivated by removal of the drugs. Our data highlight an integral role for SIK2 and SIK3 in innate immunity by preventing the differentiation of macrophages into a potent and stable anti-inflammatory phenotype.

scholarly journals Proand anti-inflammatory cytokines in children with various clinical forms of chronic glomerulonephritis

2017 ◽  
Vol 98 (6) ◽  
pp. 943-948
Author(s):  
R O Beglyarov
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 1Β ◽  
Interleukin 4 ◽  
Chronic Glomerulonephritis ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

Aim. Study of the level of pro- and anti-inflammatory cytokines, their relationship and changes, depending on the activity of various variants of chronic glomerulonephritis in children. Methods. 104 children with nephrotic form of chronic glomerulonephritis (group 1), 9 children with hematuric form (group 2) and 88 children with mixed form (group 3) were examined. The average age of children was 10.63±3.88 years. The remission was observed in 130 (45.1%), exacerbation - in 158 (54.9%) patients. The concentration of proinflammatory (interleukin-1β, -8, tumor necrosis factor α, interferon γ) and anti-inflammatory cytokines (interleukin-10 and -4) was determined in the blood by ELISA. Results. A significant increase in the levels of interleukin-1β and -8, tumor necrosis factor α, interferon γ was revealed. The index of cytokines in nephrotic and mixed variant was 2.6 standard units, in hematuric form - 2.5 standard units. More pronounced imbalance of pro- and anti-inflammatory cytokines was revealed in nephrotic and mixed forms of chronic glomerulonephritis. Regardless of the form, an increase was revealed in the ratio of interleukin-1β/interleukin-4 (p <0.05), tumor necrosis factor α/interleukin-4 and tumor necrosis factor α/interleukin-10 (p <0.01). Conclusion. Children with different clinical variants of chronic glomerulonephritis were found to have imbalance of cytokines with the shift towards predominance of proinflammatory cytokines; the most pronounced differences were observed in the content of interleukin-1β and tumor necrosis factor α; both in exacerbation and remission phases cytokine index is higher than 1 which is indicative of active inflammatory process.

scholarly journals Characteristics of cytokine status in the pathogenesis of experimental periodontitis and immobilization stress

2021 ◽  
Vol 11 (8) ◽  
pp. 504-509
Author(s):  
P. Olekshij
Keyword(s):  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Immobilization Stress ◽  
Interleukin 10 ◽  
Tnf Α ◽  
Experimental Periodontitis ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

The aim of our study is to elucidate changes in the content of pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokines interleukin-10 (IL-10) in the blood serum of guinea pigs in the dynamics of experimental periodontitis and immobilization stress.The dynamics of the combined pathology (experimental periodontitis and immobilization stress) is accompanied by a pronounced progression of the proinflammatory group of cytokines - TNF-α and IL-6 against the background of declining functional activity of IL-10 at all stages of their formation (3 rd , 5 th and 15 th days) with an advantage on the 15 th day of the experiment. The data obtained indicate an imbalance of pro- and anti-inflammatory cytokines and impaired cytokinogenesis, which is important for the pathogenesis in this combined pathology.

scholarly journals Pro-Inflammatory Cytokines at Ultra-Low Dose Exert Anti-Inflammatory Effect In Vitro: A Possible Mode of Action Involving Sub-Micron Particles?

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582096172
Author(s):  
Ilaria Floris ◽  
Thorsten Rose ◽  
Juan Antonio Collado Rojas ◽  
Kurt Appel ◽  
Camille Roesch ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Mode Of Action ◽  
Inflammatory Diseases ◽  
Resistive Pulse ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are pro-inflammatory cytokines involved in acute and chronic inflammatory diseases. Indeed, immunotherapy blocking these 2 cytokines has been developed. Micro-immunotherapy (MI) also uses ultra-low doses (ULD) of pro-inflammatory cytokines, impregnated on lactose-sucrose pillules, to counteract their overexpression. The study has been conducted with 2 objectives: examine the anti-inflammatory effect in vitro and the capacity of 2 unitary medicines, TNF-α (27 CH) and IL-1β (27 CH), to reduce the secretion of TNF-α in human primary monocytes and THP-1 cells differentiated with phorbol-12-myristate-13-acetate, after lipopolysaccharide (LPS) exposure; then, investigate the presence of particles possibly containing starting materials using tunable resistive pulse sensing technique. The results show that the unitary medicines, tested at 3 pillules concentrations (5.5, 11 and 22 mM), have reduced the secretion of TNF-α in both models by about 10−20% vs. vehicle control, depending on concentration. In this exploratory study, particles (150−1000 nm) have been detected in MI ULD-impregnated pillules and a hypothesis for MI medicines mode of action has been proposed. Conscious that more evaluations are necessary, authors are cautious in the conclusions because the findings described in the study are still limited, and future investigations may lead to different hypothesis.

scholarly journals Acyclic Triterpenoid Isolated from Alpinia katsumadai Alleviates Formalin-Induced Chronic Mouse Paw Inflammation by Inhibiting the Phosphorylation of ERK and NF-κB

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3345 ◽  
Author(s):  
Hyung Jin Lim ◽  
Seon Gyeong Bak ◽  
Hee Ju Lim ◽  
Seung Woong Lee ◽  
Soyoung Lee ◽  
...  
Keyword(s):  
Mouse Model ◽  
Inflammatory Diseases ◽  
Extracellular Signal ◽  
Tnf Α ◽  
J774 Cells ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.

scholarly journals ABIN1 alleviates inflammatory responses and colitis via facilitating A20 activity

2020 ◽  
Vol 11 ◽  
pp. 204062232094478
Author(s):  
Tian Pu ◽  
Wenzheng Liu ◽  
Yijun Wu ◽  
Ye Zhao
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Myeloid Cell ◽  
Protein Levels ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Background: Macrophages-mediated inflammation is involved in the progress of colitis. The present study aims to explore the roles of A20-binding inhibitor of NF-κB (ABIN1) in the macrophages and its underlying mechanisms. Methods: ABIN1 myeloid cell-conditional transgenic mice were established and genotyped by PCR and immunoblotting assays. Tumor necrosis factor (TNF)-α was applied to pre-treat bone marrow-derived macrophages (BMDMs) in the presence of lipopolysaccharide. The mRNA and protein levels of pro-inflammatory cytokines were determined by qRT-PCR and ELISA, respectively. Dextran sulfate sodium (DSS)-induced colitis was established to determine the effects of ABIN1 on the survival time, body weight, colon length, and colon histopathological changes. Western blotting was applied to determine the expressions of signaling proteins. Results: ABIN1 overexpression did not affect cell populations of macrophages and neutrophils in mice. Its overexpression reduced the productions of pro-inflammatory cytokines in BMDMs and ameliorated survival rate and colitis symptoms in the DSS-induced mouse model. The underlying mechanisms revealed that ABIN1 impaired macrophages-mediated inflammatory responses, in part by regulating the NF-κB signal pathway, and its ameliorated effects on the symptoms of DSS-induced colitis were associated with A20/tumor necrosis factor α-induced protein 3 (TNFAIP3). Conclusion: ABIN1 attenuated inflammatory responses and colitis by regulating A20/TNFAIP3 activities.

scholarly journals Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 72 ◽  
Author(s):  
Abdulmalik Alqarni ◽  
Valerie Ferro ◽  
John Parkinson ◽  
Mark Dufton ◽  
David Watson
Keyword(s):  
Inflammatory Cytokines ◽  
Cell Activation ◽  
Flash Chromatography ◽  
System Response ◽  
Macrophage Cell ◽  
Tnf Α ◽  
Immune System Response ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Melittin, the major active peptide of honeybee venom (BV), has potential for use in adjuvant immunotherapy. The immune system response to different stimuli depends on the secretion of different metabolites from macrophages. One potent stimulus is lipopolysaccharide (LPS), a component isolated from gram-negative bacteria, which induces the secretion of pro-inflammatory cytokines in macrophage cell cultures. This secretion is amplified when LPS is combined with melittin. In the present study, pure melittin was isolated from whole BV by flash chromatography to obtain pure melittin. The ability of melittin to enhance the release of tumour necrosis factor-α (TNF-α), Interleukin (IL-1β, IL-6, and IL-10) cytokines from a macrophage cell line (THP-1) was then assessed. The response to melittin and LPS, applied alone or in combination, was characterised by metabolic profiling, and the metabolomics results were used to evaluate the potential of melittin as an immune adjuvant therapy. The addition of melittin enhanced the release of inflammatory cytokines induced by LPS. Effective chromatographic separation of metabolites was obtained by liquid chromatography-mass spectrometry (LC-MS) using a ZIC-pHILIC column and an ACE C4 column. The levels of 108 polar and non-polar metabolites were significantly changed (p ˂ 0.05) following cell activation by the combination of LPS and melittin when compared to untreated control cells. Overall, the findings of this study suggested that melittin might have a potential application as a vaccine adjuvant.

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