scholarly journals Techniques to Study Inflammasome Activation and Inhibition by Small Molecules

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1704
Author(s):  
Diego Angosto-Bazarra ◽  
Cristina Molina-López ◽  
Alejandro Peñín-Franch ◽  
Laura Hurtado-Navarro ◽  
Pablo Pelegrín
Keyword(s):  
Inflammatory Response ◽  
Small Molecules ◽  
Mechanism Of Action ◽  
Inflammatory Diseases ◽  
Inflammasome Activation ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory ◽  
Inhibitory Molecules ◽  
Inflammasome Inhibitors

Inflammasomes are immune cytosolic oligomers involved in the initiation and progression of multiple pathologies and diseases. The tight regulation of these immune sensors is necessary to control an optimal inflammatory response and recover organism homeostasis. Prolonged activation of inflammasomes result in the development of chronic inflammatory diseases, and the use of small drug-like inhibitory molecules are emerging as promising anti-inflammatory therapies. Different aspects have to be taken in consideration when designing inflammasome inhibitors. This review summarizes the different techniques that can be used to study the mechanism of action of potential inflammasome inhibitory molecules.

scholarly journals Endogenous galectins and the control of the host inflammatory response

2009 ◽  
Vol 201 (2) ◽  
pp. 169-184 ◽  
Author(s):  
Lucy V Norling ◽  
Mauro Perretti ◽  
Dianne Cooper
Keyword(s):  
Drug Discovery ◽  
Inflammatory Response ◽  
Inflammatory Diseases ◽  
Molecular Targets ◽  
Innovative Drug ◽  
New Era ◽  
Chronic Inflammatory Diseases ◽  
Endogenous Lectins ◽  
Anti Inflammatory ◽  
Host Inflammatory Response

A new era of research is being devoted to deciphering endogenous mediators and mechanisms that are in place to resolve the inflammatory response. Accruing evidence indicates that galectins fall into this category of immunoregulatory mediators signifying their use as prospective novel anti-inflammatory agents. The focus of this review is to depict the immunoregulatory bioactivities of three members of the galectin superfamily, Galectin (Gal)-1, Gal-3 and Gal-9. Emphasis is given to the studies investigating the properties of these endogenous lectins. Gal-1, Gal-3 and Gal-9 are emerging as pertinent players in the modulation of acute and chronic inflammatory diseases, autoimmunity and cancer, and thus being increasingly recognised as molecular targets for innovative drug discovery.

scholarly journals p38/AP-1 Pathway in Lipopolysaccharide-Induced Inflammatory Responses Is Negatively Modulated by Electrical Stimulation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Deok Jeong ◽  
Jaehwi Lee ◽  
Young-Su Yi ◽  
Yanyan Yang ◽  
Kyoung Won Kim ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Physiological Role ◽  
Peritoneal Macrophages ◽  
Cellular Level ◽  
Transcriptional Level ◽  
Weak Current ◽  
Anti Inflammatory

Electrical stimulation with a weak current has been demonstrated to modulate various cellular and physiological responses, including the differentiation of mesenchymal stem cells and acute or chronic physical pain. Thus, a variety of investigations regarding the physiological role of nano- or microlevel currents at the cellular level are actively proceeding in the field of alternative medicine. In this study, we focused on the anti-inflammatory activity of aluminum-copper patches (ACPs) under macrophage-mediated inflammatory conditions. ACPs generated nanolevel currents ranging from 30 to 55 nA in solution conditions. Interestingly, the nanocurrent-generating aluminum-copper patches (NGACPs) were able to suppress both lipopolysaccharide-(LPS-) and pam3CSK-induced inflammatory responses such as NO and PGE2production in both RAW264.7 cells and peritoneal macrophages at the transcriptional level. Through immunoblotting and immunoprecipitation analyses, we found that p38/AP-1 could be the major inhibitory pathway in the NGACP-mediated anti-inflammatory response. Indeed, inhibition of p38 by SB203580 showed similar inhibitory activity of the production of TNF-αand PGE2and the expression of TNF-αand COX-2 mRNA. These results suggest that ACP-induced nanocurrents alter signal transduction pathways that are involved in the inflammatory response and could therefore be utilized in the treatment of various inflammatory diseases such as arthritis and colitis.

scholarly journals Tackling Chronic Inflammation with Withanolide Phytochemicals—A Withaferin A Perspective

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1107
Author(s):  
Emilie Logie ◽  
Wim Vanden Berghe
Keyword(s):  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Withaferin A ◽  
Related Factor ◽  
Nuclear Factor ◽  
Pharmaceutical Drugs ◽  
In Vivo Models ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory

Chronic inflammatory diseases are considered to be one of the biggest threats to human health. Most prescribed pharmaceutical drugs aiming to treat these diseases are characterized by side-effects and negatively affect therapy adherence. Finding alternative treatment strategies to tackle chronic inflammation has therefore been gaining interest over the last few decades. In this context, Withaferin A (WA), a natural bioactive compound isolated from Withania somnifera, has been identified as a promising anti-cancer and anti-inflammatory compound. Although the majority of studies focus on the molecular mechanisms of WA in cancer models, recent evidence demonstrates that WA also holds promise as a new phytotherapeutic agent against chronic inflammatory diseases. By targeting crucial inflammatory pathways, including nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2 related factor 2 (Nrf2) signaling, WA suppresses the inflammatory disease state in several in vitro and preclinical in vivo models of diabetes, obesity, neurodegenerative disorders, cystic fibrosis and osteoarthritis. This review provides a concise overview of the molecular mechanisms by which WA orchestrates its anti-inflammatory effects to restore immune homeostasis.

STUDY OF SPECIFIC PHARMACOLOGICAL ACTIVITY OF SODIUM SALT (4-О-Β-GLUCOPYRANOSYLOXY)-BENZOIC ACID

2016 ◽  
Vol 78 (6-8) ◽  
Author(s):  
Smirnov Ivan ◽  
Murashko Tatyana ◽  
Ivanov Alex ◽  
Bondarev Alex ◽  
Udut Vladimir
Keyword(s):  
Benzoic Acid ◽  
Analgesic Activity ◽  
Sodium Salt ◽  
Analgesic Effect ◽  
Inflammatory Diseases ◽  
Peptic Ulcers ◽  
Chronic Inflammatory Diseases ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Chronic inflammatory diseases of various genesis are prevalent today. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation, but their long-term use is associated with complications in the gastrointestinal tract, including peptic ulcers. We synthesized a molecule of sodium salt (4-О-β-glucopyranosyloxy)-benzoic acid. This substance has diuretic and anti-inflammatory activities. It should be noted that most of NSAIDs has analgesic effect. In this connection, the aim of this study was to evaluate the analgesic activity of sodium salt (4-О-β-glucopyranosyloxy)-benzoic acid. We studied analgesic effect in the test “acetic writhing”. Sodium salt (4-О-β-glucopyranosyloxy)-benzoic acid significantly reduces the number of writhing by 14 units during the experiment, as an alternative criterion percent of animals with analgesia was 42.6%. Thus, in the test "acetic writhing" revealed the presence of the analgesic activity have developed drug average severity. 

scholarly journals Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

2021 ◽  
Vol 8 ◽  
Author(s):  
Yufei Xie ◽  
Annemarie H. Meijer ◽  
Marcel J. M. Schaaf
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Model Systems ◽  
Trinitrobenzene Sulfonic Acid ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses in vivo at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.

scholarly journals Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6238
Author(s):  
Paromita Sarbadhikary ◽  
Blassan P. George ◽  
Heidi Abrahamse
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
In Vivo Studies ◽  
Inflammasome Activation ◽  
Inflammatory Disorders ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.

scholarly journals Sinapic Acid Controls Inflammation by Suppressing NLRP3 Inflammasome Activation

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2327
Author(s):  
Eun Hye Lee ◽  
Jin Hak Shin ◽  
Seon Sook Kim ◽  
Su Ryeon Seo
Keyword(s):  
Cinnamic Acid ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Endotoxic Shock ◽  
Sinapic Acid ◽  
Inflammasome Activation ◽  
Cinnamic Acid Derivative ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

A natural phenolic acid compound, sinapic acid (SA), is a cinnamic acid derivative that contains 3,5-dimethoxyl and 4-hydroxyl substitutions in the phenyl ring of cinnamic acid. SA is present in various orally edible natural herbs and cereals and is reported to have antioxidant, antitumor, anti-inflammatory, antibacterial, and neuroprotective activities. Although the anti-inflammatory function of SA has been reported, the effect of SA on the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome has not been explored. In the present study, to elucidate the anti-inflammatory mechanism of SA, we examined whether SA modulates the NLRP3 inflammasome. We found that SA blocked caspase-1 activation and IL-1β secretion by inhibiting NLRP3 inflammasome activation in bone marrow-derived macrophages (BMDMs). Apoptosis-associated speck-like protein containing CARD (ASC) pyroptosome formation was consistently blocked by SA treatment. SA specifically inhibited NLRP3 activation but not the NLRC4 or AIM2 inflammasomes. In addition, SA had no significant effect on the priming phase of the NLRP3 inflammasome, such as pro-IL-1β and NLRP3 inflammasome expression levels. Moreover, we found that SA attenuated IL-1β secretion in LPS-induced systemic inflammation in mice and reduced lethality from endotoxic shock. Our findings suggest that the natural compound SA has potential therapeutic value for the suppression of NLRP3 inflammasome-associated inflammatory diseases.

Abstract 1290: Development of anti inflammatory agents targeting TonEBP for treatment of chronic inflammatory diseases

2019 ◽  
Author(s):  
Byeongjin YE ◽  
Hyug Moo Kwon ◽  
Soo Youn Choi ◽  
Jun Ho Lee ◽  
Hyun Je Kang ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory

scholarly journals Action of the 4-Nitro-2-phenoximethanesulphonanilide (Nimesulide) on neutrophil chemotaxis and superoxide production

1994 ◽  
Vol 112 (1) ◽  
pp. 489-494 ◽  
Author(s):  
Susana Beatriz Veríssimo de Mello ◽  
leda Maria Magalhães Laurindo ◽  
Wilson Cossermelli
Keyword(s):  
Inflammatory Response ◽  
Peripheral Blood ◽  
Superoxide Anion ◽  
Healthy Subjects ◽  
Inflammatory Diseases ◽  
Neutrophil Function ◽  
Neutrophil Chemotaxis ◽  
Inflammatory Agent ◽  
Blood Neutrophils ◽  
Anti Inflammatory

4-nitro-2-phenoximethanesulphonanilide (nimesulide) is a nonsteroidal anti-inflammatory agent that has been employed in the treatment of inflammatory diseases because of its specific actions on the inflammatory response mechanisms caused by injury. The objectives of this paper were to determine the action of this agent on two notable neutrophil functions, chemotaxis and production of the superoxide anion. These two functions were studied after the neutrophils were pre-incubated with three different concentrations of 4-nitro-2-phenoximethanesulphonanilide (0.1; 0.3 and 0.5 mN). The results obtained herein demonstrated that 4-nitro-2-phenoximethanesulphonanilide-exposed peripheral blood neutrophils from healthy subjects produced significantly less superoxide when challenged by phorbol-mirystate acetate (PMA at 50 ng/ml) or formy-methionil-leucyl-phenilalanine (FMLP 10 -7 M) and opsonizided zymozan (1 mg/ml). Additionally, the agent was equally effective in reducing the PMN chemotoaxis when challenged by C5a factor (2% zimozan activated solution), FMLP 10 -9 M and leukotrien (3. 10 -7 M). The results obtained suggest that in addition to its interference in the metabolism of the aracdonic acid, the 4-nitro-2 phenoximethanesulphonanilide may interfere in a more direct fashion with the neutrophil function. This specific action may contribute to its anti-inflammatory activity.

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