Parthenolide ameliorates Concanavalin A-induced acute hepatitis in mice and modulates the macrophages to an anti-inflammatory state

During the last few years, a significant number of studies have attempted to clarify the underlying mechanisms that lead to the presentation of atrial fibrillation (AF). Inflammation is a key component of the pathophysiological processes that lead to the development of AF; the amplification of inflammatory pathways triggers AF, and, in tandem, AF increases the inflammatory state. Indeed, the plasma levels of several inflammatory biomarkers are elevated in patients with AF. In addition, the levels of specific inflammatory biomarkers may provide information regarding to the AF duration. Several small studies have assessed the role of anti-inflammatory treatment in atrial fibrillation but the results have been contradictory. Large-scale studies are needed to evaluate the role of inflammation in AF and whether anti-inflammatory medications should be routinely administered to patients with AF.

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Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

Pharmaceutics ◽

10.3390/pharmaceutics13070991 ◽

2021 ◽

Vol 13 (7) ◽

pp. 991

Author(s):

Melanie S. Matos ◽

José D. Anastácio ◽

Cláudia Nunes dos Santos

Keyword(s):

Biological Activities ◽

Sesquiterpene Lactones ◽

Physiological State ◽

Plant Secondary Metabolites ◽

Inflammatory Pathways ◽

Inflammatory State ◽

Anti Inflammatory ◽

Inflammatory Molecules

Inflammation is a crucial and complex process that reestablishes the physiological state after a noxious stimulus. In pathological conditions the inflammatory state may persist, leading to chronic inflammation and causing tissue damage. Sesquiterpene lactones (SLs) are composed of a large and diverse group of highly bioactive plant secondary metabolites, characterized by a 15-carbon backbone structure. In recent years, the interest in SLs has risen due to their vast array of biological activities beneficial for human health. The anti-inflammatory potential of these compounds results from their ability to target and inhibit various key pro-inflammatory molecules enrolled in diverse inflammatory pathways, and prevent or reduce the inflammatory damage on tissues. Research on the anti-inflammatory mechanisms of SLs has thrived over the last years, and numerous compounds from diverse plants have been studied, using in silico, in vitro, and in vivo assays. Besides their anti-inflammatory potential, their cytotoxicity, structure–activity relationships, and pharmacokinetics have been investigated. This review aims to gather the most relevant results and insights concerning the anti-inflammatory potential of SL-rich extracts and pure SLs, focusing on their effects in different inflammatory pathways and on different molecular players.

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In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

Scientific Reports ◽

10.1038/s41598-021-94228-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rosangela Montanaro ◽

Alessio D’Addona ◽

Andrea Izzo ◽

Carlo Ruosi ◽

Vincenzo Brancaleone

Keyword(s):

Inflammatory Markers ◽

In Vitro Study ◽

Inos Expression ◽

Beneficial Effects ◽

Tnf Α ◽

Inflammatory State ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

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Perfluorocarbon attenuates response of concanavalin A-stimulated mononuclear blood cells without altering ligand-receptor interaction

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00432.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. L210-L216 ◽

Cited By ~ 7

Author(s):

Dirk Haufe ◽

Thomas Luther ◽

Matthias Kotzsch ◽

Lilla Knels ◽

Thea Koch

Keyword(s):

Cell Surface ◽

Concanavalin A ◽

Blood Cells ◽

Cell Activation ◽

Receptor Interaction ◽

Surface Binding ◽

Cellular Activation ◽

Flow Cytofluorometry ◽

Anti Inflammatory ◽

Mononuclear Blood Cells

Intrapulmonary application of perfluorocarbons (PFC) in acute lung injury is associated with anti-inflammatory effects. A direct impact on leukocytic function may be involved. To further elucidate PFC effects on cellular activation, we compared in an in vitro model the response of concanavalin A (ConA)-stimulated lymphocytes and monocytes exposed to perfluorohexane. We hypothesized that perfluorohexane attenuates the action of the lectin ConA by altering stimulant-receptor interaction on the cell surface. Mononuclear blood cells were stimulated by incubation with ConA in the presence of different amounts of perfluorohexane. The response of lymphocytes and monocytes was determined by means of IL-2 secretion and tissue factor (TF) expression, respectively. The influence of perfluorohexane on cell-surface binding of fluorescence-labeled ConA was studied using flow cytofluorometry and fluorescence microscopy. Perfluorohexane itself did not induce a cellular activation but significantly inhibited both monocytic TF expression and, to a far greater extent, IL-2 secretion of ConA-stimulated mononuclear blood cells. The effect of perfluorohexane was due neither to an alteration of cell viability nor to a binding of the stimulant. The amount of cell surface-bound ConA was not altered by perfluorohexane, and the overall pattern of ConA receptor rearrangement did not differ between controls and treated cells. In the present study, we provide further evidence for an anti-inflammatory effect of PFC that might be beneficial in states of pulmonary hyperinflammation. A PFC-induced alteration of stimulant-receptor interaction on the surface membrane does not seem to be the cause of attenuated cell activation.

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Monitoring liver macrophages using nanobodies targeting Vsig4: Concanavalin A induced acute hepatitis as paradigm

Immunobiology ◽

10.1016/j.imbio.2014.09.018 ◽

2015 ◽

Vol 220 (2) ◽

pp. 200-209 ◽

Cited By ~ 14

Author(s):

Fang Zheng ◽

Nick Devoogdt ◽

Amanda Sparkes ◽

Yannick Morias ◽

Chloé Abels ◽

...

Keyword(s):

Acute Hepatitis ◽

Concanavalin A ◽

Liver Macrophages

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Autophagy Induction in T Cell-Independent Acute Hepatitis Induced by Concanavalin a in SCID/NOD Mice

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200802100406 ◽

2008 ◽

Vol 21 (4) ◽

pp. 817-826 ◽

Cited By ~ 20

Author(s):

C-P. Chang ◽

H-Y. Lei

Keyword(s):

T Cell ◽

Acute Hepatitis ◽

Concanavalin A ◽

Specific Binding ◽

Nod Mice ◽

Con A ◽

Interacting Protein ◽

Autophagy Induction ◽

Adenovirus E1b ◽

Immunocompetent Mice

Concanavalin A (Con A) is known to induce acute hepatitis that is mediated by activation of NKT- and T-cell and cytokine production in immunocompetent mice. The observation of Con A-induced autophagic cell death of hepatoma cells via a Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 mediated autophagic pathway made us re-evaluate the effect of Con A-induced hepatitis in mice. Con A was administrated intravenously to BABL/c, SCID, or SCID/NOD mice at doses of 20, 30 or 40 mg/kg, respectively, to induce acute hepatitis. The levels of hepatitis and autophagy induction were both analyzed. We found that Con A can induce acute hepatitis in SCID or SCID/NOD mice with a kinetics similar to that of BALB/c, but requiring a higher dose of Con A. No lymphocyte infiltrations were found in SCID or SCID/NOD mice, and the cytokine productions were different. An autophagy with microtubule-associated protein light chain 3-II conversion was demonstrated in the liver post-Con A injection in SCID/NOD mice. Due to the mannose/glucose-specific binding on cell membrane, Con A can induce a T-cell-independent acute hepatitis with autophagy in SCID/NOD mice.

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Protective effect of pterostilbene on concanavalin A-induced acute liver injury

Food & Function ◽

10.1039/c9fo01405e ◽

2019 ◽

Vol 10 (11) ◽

pp. 7308-7314 ◽

Cited By ~ 4

Author(s):

Jiayan Wu ◽

Mengmeng Li ◽

Jingwen He ◽

Ke Lv ◽

Meiyan Wang ◽

...

Keyword(s):

Liver Injury ◽

Protective Effect ◽

Concanavalin A ◽

Acute Liver Injury ◽

Anti Inflammatory

Pterostilbene (PTE) is broadly found in berries and has antioxidant and anti-inflammatory properties.

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Renewed Avenues through Exercise Muscle Contractility and Inflammatory Status

The Scientific World JOURNAL ◽

10.1100/2012/584205 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Nelo Eidy Zanchi ◽

Felipe Natali Almeida ◽

Fábio Santos Lira ◽

José César Rosa Neto ◽

Humberto Nicastro ◽

...

Keyword(s):

Physical Inactivity ◽

Acute Exercise ◽

Inflammatory Diseases ◽

Complex Mixture ◽

Mechanical Stimulus ◽

Practical Applications ◽

Adaptive Intervention ◽

Inflammatory Status ◽

Inflammatory State ◽

Anti Inflammatory

Physical inactivity leads to the accumulation of visceral fat and, consequently, to the activation of a network of inflammatory pathways which may promote development of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. These conditions belong to the “diseasome of physical inactivity”. In contrast, the protective effect of regular exercise against diseases associated with chronic inflammation may to some extent be ascribed to an anti-inflammatory effect. The so called “acute exercise threshold”, the complex mixture of several variables involved in exercise, such as type, volume, frequency, and intensity range is capable of inducing positive physiological adaptations and has been specifically addressed in the recent literature. The major concern is related to the level of the threshold: “exercise training shifts from a therapeutic adaptive intervention to one with potential pathological consequences”. Nonetheless, if the mechanical stimulus is too weak to disrupt cellular homeostasis, training adaptations will not occur. Answering these questions could present practical applications, especially during inflammatory diseases associated with detrimental muscle effects and could theoretically constitute a “new” therapeutic approach to treat/improve an inflammatory state. This paper aims to describe specific data from the literature regarding the effects of exercise on inflammatory diseases in order to promote a more sophisticated perspective on the anti-inflammatory effects of exercise.

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