The mechanism of aspirin

2018 ◽  
Author(s):  
Pierre Sirois ◽  
Pedro D’Orléans-Juste
Keyword(s):  
Beneficial Effect ◽  
Mechanism Of Action ◽  
Inflammatory Diseases ◽  
Tissue Homogenates ◽  
Willow Tree

Aspirin has been used for the treatment of pain and inflammation for more than a hundred years; however, the medical use of what we now called aspirin dates back to antiquity, since willow-tree extracts containing salicylates were described in the Egyptian pharmacopoeia around 1543 bc. In 1971, Sir John Vane and his collaborators discovered its mechanism of action. This discovery has generated tremendous interest into the beneficial effect of this drug for the treatment of pain, inflammation, many inflammatory diseases, and even cancers. Vane and his collaborators also tested a number of other well-known aspirin-like drugs, or NSAIDs (for non-steroid anti-inflammatory drugs), and found that they all inhibited to a different extent the release of prostaglandins from organs as well as from tissue homogenates.

Pharmacologic activities of phytosteroids in inflammatory diseases: Mechanism of action and therapeutic potentials

2021 ◽  
Author(s):  
Rishab Marahatha ◽  
Kabita Gyawali ◽  
Kabita Sharma ◽  
Narayan Gyawali ◽  
Parbati Tandan ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Inflammatory Diseases

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 A histochemical approach to the mechanism of action of cisplatin and its analogues.

1993 ◽  
Vol 41 (7) ◽  
pp. 1053-1073 ◽  
Author(s):  
S K Aggarwal
Keyword(s):  
Membrane Transport ◽  
Mechanism Of Action ◽  
Morphological Changes ◽  
Calcium Supplementation ◽  
Rat Kidney ◽  
Light And Electron Microscopy ◽  
Atp Synthesis ◽  
Chloride Ion ◽  
Tissue Homogenates ◽  
Cancer Agent

The effects of cisplatin (CDDP), a potent anti-cancer agent, and its various analogues were analyzed for any biochemical changes involving Ca2+ and lysosomal and membrane-associated transport enzymes in rat kidney, liver, serum, urine, tissue homogenates, and isolated mitochondria. Correlation was made with any morphological changes observed by light and electron microscopy to gain an insight into the mechanism of action of various platinum coordination complexes. CDDP in its hydrolyzed state under conditions of low chloride ion concentrations causes uncoupling of oxidative phosphorylation, calcium efflux from the mitochondria, inhibits ATP synthesis, lowers membrane-associated calcium and various membrane transport enzymes, and induces an increase in the number of lysosomes. Enzymes such as alkaline phosphatase are stripped from the brush borders of the proximal tubule cells and are discharged in the urine. However, daily IV injections of calcium (1.1 ml of 1.3% CaCl2) supplementation protect the membrane-associated enzymes from cisplatin action. Carboplatin (CBDCA), an analogue of CDDP and the least nephrotoxic of all its analogues, shows little effect on the membrane-associated transport enzymes. Therefore, cisplatin and its various analogues seem to affect the membrane transport enzymes to varying degrees with related nephrotoxicity. Calcium supplementation seems to protect these enzymes and preserve kidney function.

Mineralocorticoid receptor antagonists

ESC CardioMed ◽  
2018 ◽  
pp. 167-173
Author(s):  
Faiez Zannad ◽  
João Pedro Ferreira
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Adverse Effects ◽  
Beneficial Effect ◽  
Mechanism Of Action ◽  
Mineralocorticoid Receptor ◽  
Post Myocardial Infarction ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Clinical Syndromes

Hypertension, post-myocardial infarction, and heart failure are the cardiovascular clinical syndromes where mineralocorticoid receptor antagonists (MRAs) have shown a beneficial effect. Most guidelines while recommending a MRA do not make a clear recommendation as to which MRA should be used, how doses should be titrated, or which monitorization is indicated. This chapter provides an appraisal of the different types of MRA drugs and their pharmacological differences with respect to mechanism of action, pharmacokinetics, monitoring, adverse effects, and drug interactions.

scholarly journals The Role of Poly(ADP-ribose) Polymerase-1 in Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Samuel García ◽  
Carmen Conde
Keyword(s):  
Rheumatoid Arthritis ◽  
Septic Shock ◽  
Dna Repair ◽  
Beneficial Effect ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Genomic Stability ◽  
Inflammatory Processes ◽  
Parp 1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis.

How does methotrexate work?

2020 ◽  
Vol 48 (2) ◽  
pp. 559-567 ◽  
Author(s):  
Adel M. Alqarni ◽  
Martin P. Zeidler
Keyword(s):  
Mechanism Of Action ◽  
Low Dose ◽  
Inflammatory Diseases ◽  
Low Cost ◽  
Essential Medicine ◽  
Chemotherapy Agent ◽  
Folate Pathway ◽  
Inflammatory Mechanism ◽  
Rheumatic Drug ◽  
Stat Pathway

Developed over 70 years ago as an anti-folate chemotherapy agent, methotrexate (MTX) is a WHO ‘essential medicine’ that is now widely employed as a first-line treatment in auto-immune, inflammatory diseases such as rheumatoid arthritis (RA), psoriasis and Crone's disease. When used for these diseases patients typically take a once weekly low-dose of MTX — a therapy which provides effective inflammatory control to tens of millions of people worldwide. While undoubtedly effective, our understanding of the anti-inflammatory mechanism-of-action of low-dose MTX is incomplete. In particular, the long-held dogma that this disease-modifying anti-rheumatic drug (DMARD) acts via the folate pathway does not appear to hold up to scrutiny. Recently, MTX has been identified as an inhibitor of JAK/STAT pathway activity, a suggestion supported by many independent threads of evidence. Intriguingly, the JAK/STAT pathway is central to both the inflammatory and immune systems and is a pathway already targeted by other RA treatments. We suggest that the DMARD activity of MTX is likely to be largely mediated by its inhibition of JAK/STAT pathway signalling while many of its side effects are likely associated with the folate pathway. This insight into the mechanism-of-action of MTX opens the possibility for repurposing this low cost, safe and effective drug for the treatment of other JAK/STAT pathway-associated diseases.

scholarly journals Loss of PTPN22 abrogates the beneficial effect of cohousing-mediated fecal microbiota transfer in murine colitis

2019 ◽  
Vol 12 (6) ◽  
pp. 1336-1347
Author(s):  
Marianne R. Spalinger ◽  
Marlene Schwarzfischer ◽  
Larissa Hering ◽  
Ali Shawki ◽  
Anica Sayoc ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Protein Tyrosine Phosphatase ◽  
Genetic Background ◽  
Inflammatory Diseases ◽  
Tyrosine Phosphatase ◽  
Fecal Microbiota ◽  
Wild Type ◽  
Murine Colitis ◽  
Risk Gene ◽  
Deficient Mice

Abstract Fecal microbiota transfer (FMT) is a very efficient approach for the treatment of severe and recurring C. difficile infections. However, the beneficial effect of FMT in other disorders such as ulcerative colitis (UC) or Crohn’s disease remains unclear. Furthermore, it is currently unknown how disease-associated genetic variants in donors or recipients influence the effect of FMT. We found that bacteria-transfer from wild-type (WT) donors via cohousing was efficient in inducing recovery from colitis in WT mice, but not in mice deficient in protein-tyrosine phosphatase non-receptor type 22 (PTPN22), a known risk gene for several chronic inflammatory diseases. Also cohousing of PTPN22-deficient mice with diseased WT mice failed to induce faster recovery. Our data indicate that the genetic background of the donor and the recipient influences the outcome of microbiota transfer, and offers a potential explanation why transfer of fecal microbes from some, but not all donors is efficient in UC patients.

scholarly journals The Extract of Chrysanthemum zawadskii var. latilobum Ameliorates Collagen-Induced Arthritis in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
A-Ram Kim ◽  
Hyuk Soon Kim ◽  
Do Kyun Kim ◽  
Jun Ho Lee ◽  
Young Hyo Yoo ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Bone Erosion ◽  
Inflammatory Diseases ◽  
Osteoclast Differentiation ◽  
Human Rheumatoid Arthritis ◽  
Collagen Induced Arthritis ◽  
Mobility Shift ◽  
Chrysanthemum Zawadskii

Chrysanthemum zawadskii var. latilobum (CZ) has been used for beverage or tea and also as folk medicine for the remedy of diverse inflammatory diseases. Nevertheless, the therapeutic effect of CZ on arthritis remains to be unknown. In this paper we aim to investigate the CZ’s antiarthritic effect and mechanism of action both in vitro and in vivo. To assess CZ’s antiarthritic effect, mouse models of type II collagen-induced arthritis (CIA) were used. Mice were used to gauge clinical arthritis index and histopathological changes. Reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting, electrophoretic mobility shift assay (EMSA), and other biological methods were adopted to measure CZ’s effect on arthritis and to understand the veiled mechanism of action. CZ greatly suppressed CIA, histopathological score, bone erosion, and osteoclast differentiation. Mechanistically, CZ inhibited the production of various inflammatory and arthritic mediators like inflammatory cytokines, matrix metalloproteinases (MMPs), and chemokines. Of note, CZ significantly suppressed the activation of the NF-κB pathway in vivo. CZ exerted an antiarthritic effect in CIA mice by curbing the production of crucial inflammatory and arthritis mediators. This study warrants further investigation of CZ for the use in human rheumatoid arthritis (RA).

scholarly journals Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 389 ◽  
Author(s):  
Gregorio Martínez-Sánchez ◽  
Adriana Schwartz ◽  
Vincenzo Di Donna
Keyword(s):  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Organ Damage ◽  
Experimental Models ◽  
Ozone Therapy ◽  
Cytoprotective Activity ◽  
Target Organs

(1) Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak. Systemic ozone therapy (OT) could be potentially useful in the clinical management of several complications secondary to SARS-CoV-2. The rationale and mechanism of action has already been proven clinically in other viral infections and has been shown in research studies to be highly effective at decreasing organ damage mediated by inflammation and oxidative stress. This review summarizes the OT studies that illustrate the possible cytoprotective mechanism of action of ozone and its physiological by-products in target organs affected by SARS-CoV-2. (2) Methods: This review encompasses a total of 74 peer-reviewed original articles. It is mainly focused on ozone as a modulator of the NF-κB/Nrf2 pathways and IL-6/IL-1β expression. (3) Results: In experimental models and the few existent clinical studies, homeostasis of the free radical and antioxidant balance by OT was associated with a modulation of NF-κB/Nrf2 balance and IL-6 and IL-1β expression. These molecular mechanisms support the cytoprotective effects of OT against tissue damage present in many inflammatory diseases, including viral infections. (4) Conclusions: The potential cytoprotective role of OT in the management of organ damage induced by COVID-19 merits further research. Controlled clinical trials are needed.

IgG1 and IVIg induce inhibitory ITAM signaling through FcγRIII controlling inflammatory responses

Blood ◽  
2012 ◽  
Vol 119 (13) ◽  
pp. 3084-3096 ◽  
Author(s):  
Meryem Aloulou ◽  
Sanae Ben Mkaddem ◽  
Martine Biarnes-Pelicot ◽  
Tarek Boussetta ◽  
Hervé Souchet ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Activating Receptors ◽  
Autoimmune And Inflammatory Diseases ◽  
Continuous Interaction ◽  
Species Production ◽  
Activation Motif

Abstract Intravenous immunoglobulin (IVIg) has been used in the treatment of several autoimmune and inflammatory diseases. However, its mechanism of action remains incompletely understood. Here, we investigated the possibility that IVIg induces its anti-inflammatory effects through activating Fcγ receptors bearing an immunoreceptor tyrosine-based activation motif (ITAM) in the FcRγ signaling adaptor. Recently, the concept of inhibitory ITAM (ITAMi) has emerged as a new means to negatively control the immune response. We found that interaction of FcRγ-associated mouse or human FcγRIII with uncomplexed IgG1 or IVIg, or with bivalent anti-FcγRIII F(ab′)2 reduced calcium responses, reactive oxygen species production, endocytosis, and phagocytosis, induced by heterologous activating receptors on monocyte/macrophages and FcγRIII+ transfectants. Inhibition required the ITAMi configuration of the FcγRIII-associated FcRγ subunit and SHP-1 recruitment involving formation of intracellular “inhibisome” clusters containing FcγRIII, and the targeted heterologous activating receptor. IVIg as well as anti-FcγRIII treatments controlled the development of nonimmune mediated inflammation in vivo independently of FcγRIIB. These results demonstrate that circulating immunoglobulins (Ig)Gs are not functionally inert but act through continuous interaction with FcγRIII-inducing ITAMi signaling to maintain immune homeostasis. These data support a new mechanism of action for IVIg and demonstrate the therapeutic potential of FcγRIIIA targeting in inflammation.

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