scholarly journals Effects of non-steroidal anti-inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses. EAACI task force on eicosanoids consensus report in times of COVID-19

Author(s):  
Milena Sokolowska ◽  
G Enrico Rovati ◽  
Zuzana Diamant ◽  
Eva Untersmayr ◽  
Jürgen Schwarze ◽  
...  

Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarises currently available knowledge, novel discoveries and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarise the major knowledge gaps and unmet needs in current eicosanoid research.

2021 ◽  
Vol 14 (7) ◽  
pp. 692
Author(s):  
Ryldene Marques Duarte da Cruz ◽  
Francisco Jaime Bezerra Mendonça-Junior ◽  
Natália Barbosa de Mélo ◽  
Luciana Scotti ◽  
Rodrigo Santos Aquino de Araújo ◽  
...  

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.


2021 ◽  
Vol 28 ◽  
Author(s):  
Josiane Viana Cruz ◽  
Joaquín María Campos Rosa ◽  
Njogu Mark Kimani ◽  
Silvana Giuliatti ◽  
Cleydson Breno Rodrigues dos Santos

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.


2021 ◽  
Vol 23 (3) ◽  
Author(s):  
V. V. Buheruk ◽  
O. B. Voloshyna ◽  
L. I. Kovalchuk ◽  
I. V. Balashova ◽  
O. V. Naidionova

The aim of this review is to analyze and summarize the existing evidence regarding the possibilities of using acetylsalicylic acid (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) to reduce cancer risk. Conclusions. Chronic inflammation facilitates the onset and progress of tumour growth. Anti-cancer properties of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs are mediated via cyclooxygenase COX-dependent mechanisms, as well as other tumorigenic pathways. Current systematic review addresses potential role of ASA and other NSAIDs in reduction of cancer risk for the following localizations: head and neck, lungs, gastrointestinal tract, breast, ovaries, prostate, and skin. The role of ASA in primary prevention of colorectal cancer in specific populations is presented in 2016 U. S. Preventive Services Task Force guidelines. Studies indicate heterogeneous protective potential of ASA against different cancer types, depending on studied population, duration of intake and dose. Influence of non-aspirin NSAIDs on cancer morbidity and mortality is more controversial.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah Cristina Gozzi-Silva ◽  
Franciane Mouradian Emidio Teixeira ◽  
Alberto José da Silva Duarte ◽  
Maria Notomi Sato ◽  
Luana de Mendonça Oliveira

Nutrition is an important tool that can be used to modulate the immune response during infectious diseases. In addition, through diet, important substrates are acquired for the biosynthesis of regulatory molecules in the immune response, influencing the progression and treatment of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In this way, nutrition can promote lung health status. A range of nutrients, such as vitamins (A, C, D, and E), minerals (zinc, selenium, iron, and magnesium), flavonoids and fatty acids, play important roles in reducing the risk of pulmonary chronic diseases and viral infections. Through their antioxidant and anti-inflammatory effects, nutrients are associated with better lung function and a lower risk of complications since they can decrease the harmful effects from the immune system during the inflammatory response. In addition, bioactive compounds can even contribute to epigenetic changes, including histone deacetylase (HDAC) modifications that inhibit the transcription of proinflammatory cytokines, which can contribute to the maintenance of homeostasis in the context of infections and chronic inflammatory diseases. These nutrients also play an important role in activating immune responses against pathogens, which can help the immune system during infections. Here, we provide an updated overview of the roles played by dietary factors and how they can affect respiratory health. Therefore, we will show the anti-inflammatory role of flavonoids, fatty acids, vitamins and microbiota, important for the control of chronic inflammatory diseases and allergies, in addition to the antiviral role of vitamins, flavonoids, and minerals during pulmonary viral infections, addressing the mechanisms involved in each function. These mechanisms are interesting in the discussion of perspectives associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its pulmonary complications since patients with severe disease have vitamins deficiency, especially vitamin D. In addition, researches with the use of flavonoids have been shown to decrease viral replication in vitro. This way, a full understanding of dietary influences can improve the lung health of patients.


2016 ◽  
Vol 21 (6) ◽  
pp. 567-578 ◽  
Author(s):  
José Pérez del Palacio ◽  
Caridad Díaz ◽  
Mercedes de la Cruz ◽  
Frederick Annang ◽  
Jesús Martín ◽  
...  

It is widely accepted that central nervous system inflammation and systemic inflammation play a significant role in the progression of chronic neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury, and multiple sclerosis. Therefore, it seems reasonable to propose that the use of anti-inflammatory drugs might diminish the cumulative effects of inflammation. Indeed, some epidemiological studies suggest that sustained use of anti-inflammatory drugs may prevent or slow down the progression of neurodegenerative diseases. However, the anti-inflammatory drugs and biologics used clinically have the disadvantage of causing side effects and a high cost of treatment. Alternatively, natural products offer great potential for the identification and development of bioactive lead compounds into drugs for treating inflammatory diseases with an improved safety profile. In this work, we present a validated high-throughput screening approach in 96-well plate format for the discovery of new molecules with anti-inflammatory/immunomodulatory activity. The in vitro models are based on the quantitation of nitrite levels in RAW264.7 murine macrophages and interleukin-8 in Caco-2 cells. We have used this platform in a pilot project to screen a subset of 5976 noncytotoxic crude microbial extracts from the MEDINA microbial natural product collection. To our knowledge, this is the first report on an high-throughput screening of microbial natural product extracts for the discovery of immunomodulators.


Author(s):  
Haitham Saeed ◽  
Hasnaa Osama ◽  
Mona A. Abdelrahman ◽  
Yasmin M. Madney ◽  
Hadeer S. Harb ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19) is a viral disease that causes a respiratory disorder, started in December of 2019 in China. Several vitamins and trace elements could help in enhancing host immunity producing antioxidant or anti-inflammatory action. This work aimed to identify the role of different nutrition, vitamins, and trace elements on the immunity status of the infected subject and the possibility of the beneficial role of these elements in the management of COVID-19. Main body After collecting (PubMed, scholar, OVID, Embase, Cochrane Library) and investigating published articles, testing the effect of these elements on viral infection, it was found that most of these elements have a significant role during viral infection through a different mechanism, like antioxidant, anti-inflammatory, and immunomodulation. Nutritional interventions in COVID-19 infections are very important currently, and it was reported that vitamin C and D reduce the risk of acute respiratory infections. In addition, low vitamin A diets compromise the effectiveness of inactivated bovine coronavirus vaccines. Administration of N-acetyl cysteine showed a beneficial inhibitory effect in viral infections and enhanced glutathione production. The deficiency of selenium on COVID-19 subjects has a significant impact on the clinical outcome of the subjects. In addition, supplementation with vitamins proved to enhance immune response during viral infection. Vitamins and trace elements not only showed a beneficial effect but also Omega 3 fatty acids showed an immunomodulating effect during infections. Short conclusions Assessment of levels for these trace elements at the baseline and providing supplementation containing different vitamins and elements could result in better control and clinical outcomes in the case of COVID-19.


2016 ◽  
Vol 64 (3) ◽  
pp. 312-319
Author(s):  
Juliano CAVAGNI ◽  
Francisco Wilker Mustafa Gomes MUNIZ ◽  
Cassiano Kuchenbecker RÖSING

ABSTRACT Periodontal diseases are infecto-inflammatory diseases. Literature, has tried to elucidate the infections component of gingivitis and periodontitis, for several years. In recent years, much has been discussed about the role of the host response modulators to periodontal therapeutic procedures. The aim of the present literature review was to evaluate the effect of host response modulating agents (anti-inflammatories) on the pathogenesis of gingivitis and periodontitis. A search in the main databases was performed and human and animal studies were selected. The majority of studies was performed in humans and non-steroidal anti-inflammatory drugs in different dosages were used. The results have shown a potential benefit of the non-steroidal anti-inflammatory drugs concerning the microbial challenge. However, this benefit seems not to occur in the long term, thus not supporting it as a periodontal therapeutic approach. Few studies evaluated the effect of steroidal anti-inflammatory drugs on the pathogenesis of periodontal diseases. Moreover, the results in humans and animals are controversial, pointing to a possible deleterious effect of steroidal anti-inflammatory drugs on periodontal structures.


1996 ◽  
Vol 16 (01) ◽  
pp. 56-59
Author(s):  
D. J. Tyrrell ◽  
C. P. Page

SummaryEvidence continues to accumulate that the pleiotropic nature of heparin (beyond its anticoagulant potency) includes anti-inflammatory activities at a number of levels. It is clear that drugs exploiting these anti-inflammatory activities of heparin may offer exciting new therapeutic applications to the treatment of a wide range of inflammatory diseases.


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