scholarly journals Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor

10.1038/nm786 ◽  
2002 ◽  
Vol 8 (11) ◽  
pp. 1296-1302 ◽  
Author(s):  
Mauro Perretti ◽  
Nan Chiang ◽  
Mylinh La ◽  
Iolanda M. Fierro ◽  
Stefano Marullo ◽  
...  
Keyword(s):  
Lipoxin A4 ◽  
Inflammatory Pathways ◽  
Endogenous Lipid ◽  
Anti Inflammatory

Inflammatory Biomarkers in Atrial Fibrillation

2019 ◽  
Vol 26 (5) ◽  
pp. 837-854 ◽  
Author(s):  
Effimia Zacharia ◽  
Nikolaos Papageorgiou ◽  
Adam Ioannou ◽  
Gerasimos Siasos ◽  
Spyridon Papaioannou ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Levels ◽  
Large Scale ◽  
Inflammatory Biomarkers ◽  
Inflammatory Pathways ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

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.

scholarly journals Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?

2021 ◽  
Vol 22 (8) ◽  
pp. 4207
Author(s):  
Nikola Tułowiecka ◽  
Dariusz Kotlęga ◽  
Andrzej Bohatyrewicz ◽  
Małgorzata Szczuko
Keyword(s):  
Ischemic Stroke ◽  
Cardiovascular Diseases ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
The Body ◽  
Brain Barrier ◽  
Lipoxin A4 ◽  
Stroke Treatment ◽  
Blood Brain ◽  
Anti Inflammatory

Introduction: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins—pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. Aim: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. Material and Methods: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: ‘stroke and lipoxin’ and ‘stroke and atherosclerosis’, resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. Results: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood–brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1β, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog—BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood–brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. Conclusions: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.

scholarly journals Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

Pharmaceutics ◽  
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.

Preeclampsia is associated with a deficiency of lipoxin A4, an endogenous anti-inflammatory mediator

2014 ◽  
Vol 102 (1) ◽  
pp. 282-290.e4 ◽  
Author(s):  
Zhangye Xu ◽  
Feng Zhao ◽  
Feng Lin ◽  
Huiqiu Xiang ◽  
Ni Wang ◽  
...  
Keyword(s):  
Inflammatory Mediator ◽  
Lipoxin A4 ◽  
Anti Inflammatory

Immunomodulatory role of paliperidone in the poly(I:C) model of schizophrenia

2016 ◽  
Vol 33 (S1) ◽  
pp. s220-s221
Author(s):  
K. MacDowell ◽  
E. Munarriz-Cuezva ◽  
D. Martín-Hernández ◽  
A. Sayd ◽  
B. García-Bueno ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Inflammatory Responses ◽  
Poly I:C ◽  
Mrna Levels ◽  
Behavioral Test ◽  
Inflammatory Pathways ◽  
Anti Inflammatory ◽  
Cellular Markers ◽  
Endogenous Antioxidant

IntroductionAlterations on the innate inflammatory response may underlie the pathophysiology of psychiatric diseases, but the mechanisms implicated remain elusive. Current antipsychotics modulate pro/anti-inflammatory pathways, but the specific mechanisms involved remain elusive. One attractive possibility is the regulation of the intracellular signalling pathways of the innate immune receptors Toll-like 3 (TLR3), which triggers antiviral and inflammatory responses.AimsTo elucidate the regulatory role of paliperidone on maternal immune activation (MIA) induced alterations on TLR3 pathway and on the two emerging endogenous antiinflammatory/antioxidant mechanisms NRF2/antioxidant enzymes pathway and the cytokine milieu regulating M1/M2 polarization in microglia.MethodsPregnant mice were treated with the synthetic Toll-like Receptor 3 (TLR3) agonist Poly(I:C) in gestational day 9 and chronically treated with paliperidone (0,05 mg/kg i.p.) in adult offspring. Animals were sacrificed one day after treatment and behavioral test. Inflammation oxidative stress-related mediators were analysed at mRNA and protein level in prefrontal cortex samples. In addition, behavioral test t-maze was conducted.ResultsPaliperidone prevented TLR3 pathway activation and the subsequent MIA-induced neuroinflammatory response. Also, paliperidone induced an increment in the activity and protein expression of nuclear NRF2, as well as increased mRNA levels of the antioxidant enzymes HO1, SOD and catalase in the MIA model. Otherwise, paliperidone increases the antiinflammatory cytokines levels TGFβ and IL-10 in favour of a M2 microglia profile and increased the levels of the M2 cellular markers ArgI and FOLR2.ConclusionsThe modulation of neuroinflammation and enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Dysregulation of prostaglandins, leukotrienes and lipoxin A4 in bronchiectasis

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216475
Author(s):  
Pallavi Bedi ◽  
Kerstin Ziegler ◽  
Phil D Whitfield ◽  
Donald Davidson ◽  
Adriano Giorgio Rossi ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Severe Disease ◽  
Stable State ◽  
Lavage Fluid ◽  
Forced Expiratory Volume ◽  
Lipid Mediators ◽  
Prostaglandin E ◽  
Lipoxin A4 ◽  
Bacterial Killing ◽  
Anti Inflammatory

IntroductionBronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay of anti-inflammatory and proinflammatory lipid mediators could lead to the development of novel anti-inflammatory therapies for bronchiectasis.AimThe aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state.MethodsSix healthy volunteers, 10 patients with mild bronchiectasis, 15 with moderate bronchiectasis and 9 with severe bronchiectasis were recruited. All participants had 60 mL of blood taken and underwent a bronchoscopy while in the stable state. Lipidomics was done on serum and bronchoalveolar lavage fluid (BALF).ResultsIn the stable state, in serum there were significantly higher levels of prostaglandin E2 (PGE2), 15-hydroxyeicosatetranoic acid (15-HETE) and leukotriene B4 (LTB4) in patients with moderate–severe disease compared with healthy volunteers. There was a significantly lower level of lipoxin A4 (LXA4) in severe bronchiectasis.In BALF, there were significantly higher levels of PGE2, 5-HETE, 15-HETE, 9-hydroxyoctadecadienoic acid and LTB4 in moderate–severe patients compared with healthy volunteers.In the stable state, there was a negative correlation of PGE2 and LTB4 with % predicted forced expiratory volume in 1 s and a positive correlation with antibiotic courses.LXA4 improved blood and airway neutrophil phagocytosis and bacterial killing in patients with bronchiectasis. Additionally LXA4 reduced neutrophil activation and degranulation.ConclusionThere is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA4 improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA4 in bronchiectasis warrants further studies.

scholarly journals Chemerin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Anthony P. Davenport ◽  
Amy E. Monaghan
Keyword(s):  
Family Member ◽  
Orphan Receptor ◽  
Resolvin D1 ◽  
Endogenous Ligand ◽  
Lipoxin A4 ◽  
Founding Family ◽  
Sequential Metabolism ◽  
Anti Inflammatory

Nomenclature for the chemerin receptors is presented as recommended by NC-IUPHAR [14, 41]). The chemoattractant protein and adipokine, chemerin, has been shown to be the endogenous ligand for both chemerin family receptors. Chemerin1 was the founding family member, and when GPR1 was de-orphanised it was re-named Chermerin2 [41]. Chemerin1 is also activated by the lipid-derived, anti-inflammatory ligand resolvin E1 (RvE1), which is formed via the sequential metabolism of EPA by aspirin-modified cyclooxygenase and lipoxygenase [2, 3]. In addition, two GPCRs for resolvin D1 (RvD1) have been identified: FPR2/ALX, the lipoxin A4 receptor, and GPR32, an orphan receptor [43].

scholarly journals Glycyrrhizic Acid for COVID-19: Findings of Targeting Pivotal Inflammatory Pathways Triggered by SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjiang Zheng ◽  
Xiufang Huang ◽  
Yanni Lai ◽  
Xiaohong Liu ◽  
Yong Jiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Interactions ◽  
Glycyrrhizic Acid ◽  
Enrichment Analysis ◽  
Host Factors ◽  
Pathway Enrichment Analysis ◽  
Protein Protein Interactions ◽  
Health Crisis ◽  
Inflammatory Pathways ◽  
Anti Inflammatory

Background: Coronavirus disease 2019 (COVID-19) is now a worldwide public health crisis. The causative pathogen is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Novel therapeutic agents are desperately needed. Because of the frequent mutations in the virus and its ability to cause cytokine storms, targeting the viral proteins has some drawbacks. Targeting cellular factors or pivotal inflammatory pathways triggered by SARS-CoV-2 may produce a broader range of therapies. Glycyrrhizic acid (GA) might be beneficial against SARS-CoV-2 because of its anti-inflammatory and antiviral characteristics and possible ability to regulate crucial host factors. However, the mechanism underlying how GA regulates host factors remains to be determined.Methods: In our report, we conducted a bioinformatics analysis to identify possible GA targets, biological functions, protein-protein interactions, transcription-factor-gene interactions, transcription-factor-miRNA coregulatory networks, and the signaling pathways of GA against COVID-19.Results: Protein-protein interactions and network analysis showed that ICAM1, MMP9, TLR2, and SOCS3 had higher degree values, which may be key targets of GA for COVID-19. GO analysis indicated that the response to reactive oxygen species was significantly enriched. Pathway enrichment analysis showed that the IL-17, IL-6, TNF-α, IFN signals, complement system, and growth factor receptor signaling are the main pathways. The interactions of TF genes and miRNA with common targets and the activity of TFs were also recognized.Conclusions: GA may inhibit COVID-19 through its anti-oxidant, anti-viral, and anti-inflammatory effects, and its ability to activate the immune system, and targeted therapy for those pathways is a predominant strategy to inhibit the cytokine storms triggered by SARS-CoV-2 infection.

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