Endothelium-Derived 5-Methoxytryptophan Is a Circulating Anti-Inflammatory Molecule That Blocks Systemic Inflammation

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

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A comparative experimental study of analgesic activity of a novel non-steroidal anti-inflammatory molecule – zaltoprofen, and a standard drug – piroxicam, using murine models

Journal of Experimental Pharmacology ◽

10.2147/jep.s212988 ◽

2019 ◽

Vol Volume 11 ◽

pp. 85-91

Author(s):

C Santenna ◽

Sunil Kumar ◽

S Balakrishnan ◽

Ratinder Jhaj ◽

Shah Newaz Ahmed

Keyword(s):

Experimental Study ◽

Analgesic Activity ◽

Murine Models ◽

Standard Drug ◽

Inflammatory Molecule ◽

Anti Inflammatory

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Anti-inflammatory Effect of Rosmarinic Acid and an Extract ofRosmarinus officinalisin Rat Models of Local and Systemic Inflammation

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/bcpt.12335 ◽

2014 ◽

Vol 116 (5) ◽

pp. 398-413 ◽

Cited By ~ 94

Author(s):

Joao Rocha ◽

Maria Eduardo-Figueira ◽

Andreia Barateiro ◽

Adelaide Fernandes ◽

Dora Brites ◽

...

Keyword(s):

Systemic Inflammation ◽

Rosmarinic Acid ◽

Rat Models ◽

Anti Inflammatory ◽

Inflammatory Effect

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Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2006.06.004 ◽

2006 ◽

Vol 66 (2) ◽

pp. 560-567 ◽

Cited By ~ 50

Author(s):

Meritxell Arenas ◽

Fèlix Gil ◽

Meritxell Gironella ◽

Víctor Hernández ◽

Sandra Jorcano ◽

...

Keyword(s):

Experimental Model ◽

Systemic Inflammation ◽

Low Dose ◽

Low Dose Radiotherapy ◽

Anti Inflammatory

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Effects of Colchicine on Measures of Lipolysis in Adults With Obesity

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.017 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A9-A10

Author(s):

Zahra Sarrafan-Chaharsoughi ◽

Jordan A Levine ◽

Tushar P Patel ◽

Sheila M Brady ◽

K Karthik Chivukula ◽

...

Keyword(s):

Systemic Inflammation ◽

Immune Cell ◽

Intravenous Glucose Tolerance Test ◽

Cell Populations ◽

Post Intervention ◽

Double Blind ◽

Immune Cell Population ◽

Intravenous Glucose ◽

Neutrophil Lymphocyte Ratio ◽

Anti Inflammatory

Abstract Background: Obesity-associated inflammation promotes adipose tissue (AT) dysfunction and contributes to the progression of type 2 diabetes and cardiovascular disease. Recent clinical studies have demonstrated that colchicine may improve metabolic and cardiovascular outcomes; however, colchicine’s effects on metabolic and inflammatory measures within AT remain unclear. Methods: The aim of this study was to examine if colchicine’s anti-inflammatory effects would improve measures of lipolysis and immune cell populations in subcutaneous AT (SAT). This is a secondary analysis of a double-blind, randomized, placebo-controlled pilot study in which 40 nondiabetic adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6mg or placebo twice daily for 3 months. Blood samples for insulin, glucose, and free fatty acids were collected in the fasted state and during a frequently-sampled intravenous glucose tolerance test. Noninsulin-suppressible (l0), insulin-suppressible (l2), and maximal (l0+l2) lipolysis rates were calculated by minimal model analysis. Body composition was determined by DXA. SAT immune cell populations were characterized by flow cytometry fluorescence-activated single cell sorting of the stromovascular fractions obtained after collagenase digestion of SAT samples obtained using a mini-liposuction technique pre- and post-intervention. Results: Data from 18 subjects in the colchicine group (Mean ± SD: age 48.4 ± 13.5 y; BMI 39.3 ± 6.3 kg/m2; sex: female 72.2%) and 18 subjects in the placebo group (age 44.7 ± 10.2 y; BMI 41.8 ± 8.2 kg/m2; sex: female 77.8%) were available for this study. Colchicine treatment significantly reduced l2 (p = 0.04) and l0+l2 (p = 0.04) versus placebo. These changes were significantly associated with reductions in systemic inflammation, including the changes in high-sensitivity C-reactive protein concentrations, white blood cell count, circulating monocyte and neutrophil populations, and the neutrophil-lymphocyte ratio (p’s < 0.015). Colchicine did not significantly alter SAT immune cell population distributions (p’s > 0.05). Conclusions: In adults with obesity and MetS, colchicine may improve insulin action at the level of AT. These improvements were positively associated with the suppression of systemic inflammation. However, no local AT inflammatory cell populations were significantly affected by colchicine use in our study, suggesting that colchicine’s systemic, rather than local, anti-inflammatory effects may be more consequential in ameliorating AT metabolic pathways in MetS. Further studies are warranted to elucidate the biological mechanisms underlying colchicine’s effects in AT, as these investigations could potentially shed light on treatments to improve metabolic outcomes in human obesity.

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Natural populations of Galphimia spp. attenuates peripheral and central inflammation

10.21203/rs.3.rs-315697/v1 ◽

2021 ◽

Author(s):

Reinier Gesto-Borroto ◽

Gabriela Meneses ◽

Alejandro Espinosa-Cerón ◽

Guillermo Granados ◽

Jacquelynne Cervantes-Torres ◽

...

Keyword(s):

Systemic Inflammation ◽

Natural Populations ◽

Inflammatory Activity ◽

Medicinal Species ◽

Methanolic Extracts ◽

Nitrite Production ◽

Anti Inflammatory ◽

Inflammatory Effect

Abstract The genus Galphimia is widely distributed in Mexico, and is represented by 22 species, including medicinal species. The sedative and anti-inflammatory effects of galphimines produced by the species Galphimia glauca have been documented. Formerly, molecular studies using DNA barcodes demonstrated that nine populations botanically classified as Galphimia glauca belong to four different species of the genus Galphimia, and that only one exhibited the sedative properties; however, all the collected species showed anti-inflammatory activity. Other bioactive compounds like quercetin, galphins, galphimidins and glaucacetalins have been identified from methanolic extracts of plants botanically classified as Galphimia glauca. The aim of this work was to determine the anti-inflammatory activity of methanolic extracts of nine collected Galphimia spp. populations grown in Mexico. The possible modes of action were analyzed by evaluating the inhibition of LPS-induced inflammation processes both in vitro and in vivo. The nine populations were evaluated by an in vitro model using RAW 264.7 murine macrophage cells, and two populations (a galphimine-producing and a non-galphimine-producing population) were selected for the in vivo experiments of systemic inflammation and neuroinflammation in mice. Results suggest that an anti-inflammatory in vitro effect was present in all the studied populations, evidenced by the inhibition of nitrite production. An inhibitory systemic inflammation in mice was exerted by the two analyzed populations. In the neuroinflammation model, the anti-inflammatory effect was demonstrated in methanolic extract of the non-galphimine-producing population. For the populations of Galphimia spp. studied herein, the anti-inflammatory effect could not be correlated to the presence of galphimines.

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Wharton’s jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00098.2018 ◽

2020 ◽

Vol 318 (1) ◽

pp. R135-R147 ◽

Cited By ~ 2

Author(s):

José Manuel Cóndor Capcha ◽

Camila Eleutério Rodrigues ◽

Roberto de Souza Moreira ◽

Marcelo Duarte Silveira ◽

Paulo Dourado ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Systemic Inflammation ◽

Cecal Ligation ◽

Wharton’S Jelly ◽

Organ Injury ◽

Experimental Sepsis ◽

Inflammatory Pathway ◽

Wharton's Jelly ◽

Anti Inflammatory

Sepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by α7-nicotinic acetylcholine receptors (α7nAChRs), which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CLP+WJ-MSCs (1 × 106 cells, at 6 h post-CLP); and CLP+methyllycaconitine (MLA)+WJ-MSCs (5 mg/kg body wt, at 5.5 h post-CLP, and 1 × 106 cells, at 6 h post-CLP, respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective α7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated α7nAChR expression, as well as reduced the phospho-STAT3-to-total STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.

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Exercise as an anti-inflammatory therapy for cancer cachexia: a focus on interleukin-6 regulation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00147.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. R296-R310 ◽

Cited By ~ 7

Author(s):

Hélène N. Daou

Keyword(s):

Skeletal Muscle ◽

Systemic Inflammation ◽

Cancer Cachexia ◽

Muscle Wasting ◽

Skeletal Muscle Atrophy ◽

Ampk Signaling ◽

Skeletal Muscle Wasting ◽

Skeletal Muscle Loss ◽

Anti Inflammatory ◽

Tumor Growth And Metastasis

Cancer cachexia is a complicated disorder of extreme, progressive skeletal muscle wasting. It is directed by metabolic alterations and systemic inflammation dysregulation. Numerous studies have demonstrated that increased systemic inflammation promotes this type of cachexia and have suggested that cytokines are implicated in the skeletal muscle loss. Exercise is firmly established as an anti-inflammatory therapy that can attenuate or even reverse the process of muscle wasting in cancer cachexia. The interleukin IL-6 is generally considered to be a key player in the development of the microenvironment of malignancy; it promotes tumor growth and metastasis by acting as a bridge between chronic inflammation and cancerous tissue and it also induces skeletal muscle atrophy and protein breakdown. Paradoxically, a beneficial role for IL-6 has also been identified recently, and that is its status as a “founding member” of the myokine class of proteins. Skeletal muscle is an important source of circulating IL-6 in people who participate in exercise training. IL-6 acts as an anti-inflammatory myokine by inhibiting TNFα and improving glucose uptake through the stimulation of AMPK signaling. This review discusses the action of IL-6 in skeletal muscle tissue dysfunction and the role of IL-6 as an “exercise factor” that modulates the immune system. This review also sheds light on the main considerations related to the treatment of muscle wasting in cancer cachexia.

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