Cyclopentenone Prostaglandins and Structurally Related Oxidized Lipid Species Instigate and Share Distinct Pro- and Anti-inflammatory Pathways

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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Activation of Endothelial Pro-resolving Anti-Inflammatory Pathways by Circulating Microvesicles from Non-muscular Myosin Light Chain Kinase-Deficient Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2016.00322 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 3

Author(s):

Abderahim Gaceb ◽

Luisa Vergori ◽

M. C. Martinez ◽

Ramaroson Andriantsitohaina

Keyword(s):

Light Chain ◽

Myosin Light Chain Kinase ◽

Myosin Light Chain ◽

Inflammatory Pathways ◽

Anti Inflammatory ◽

Deficient Mice

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

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.541 ◽

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.

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

Nature Medicine ◽

10.1038/nm786 ◽

2002 ◽

Vol 8 (11) ◽

pp. 1296-1302 ◽

Cited By ~ 307

Author(s):

Mauro Perretti ◽

Nan Chiang ◽

Mylinh La ◽

Iolanda M. Fierro ◽

Stefano Marullo ◽

...

Keyword(s):

Lipoxin A4 ◽

Inflammatory Pathways ◽

Endogenous Lipid ◽

Anti Inflammatory

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

Frontiers in Pharmacology ◽

10.3389/fphar.2021.631206 ◽

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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Lipid role in the immune system

INFORM International News on Fats Oils and Related Materials ◽

10.21748/inform.11.2021.06 ◽

2021 ◽

Vol 32 (10) ◽

pp. 6-10

Author(s):

Rebecca Guenard ◽

Keyword(s):

Fatty Acids ◽

Immune System ◽

Essential Fatty Acids ◽

The Body ◽

New Members ◽

Inflammatory Pathways ◽

Anti Inflammatory

The essential fatty acids react with enzymes to produce a group of compounds known as specialized pro-resolving mediators, or SPMs. Researchers continually discover new members of the four groups of precursors that comprise the SPM family, called lipoxins, resolvins, protectins, and maresins. These stereospecific molecules shut down inflammation and restore the body to homeostasis, a mechanism researchers are targeting for treatment as an alternative to anti-inflammatory pathways.

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Controlling Gut Inflammation by Restoring Anti-Inflammatory Pathways in Inflammatory Bowel Disease

Cells ◽

10.3390/cells8050397 ◽

2019 ◽

Vol 8 (5) ◽

pp. 397 ◽

Cited By ~ 9

Author(s):

Paolo Giuffrida ◽

Sara Cococcia ◽

Mariangela Delliponti ◽

Marco Vincenzo Lenti ◽

Antonio Di Sabatino

Keyword(s):

Inflammatory Bowel Disease ◽

Side Effects ◽

Bowel Disease ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Interleukin 10 ◽

Interleukin 12 ◽

Inflammatory Pathways ◽

Inflammatory Bowel ◽

Anti Inflammatory

Inflammatory bowel disease (IBD) is caused by a dysregulated immune response against normal components of the intestinal microflora combined with defective functioning of anti-inflammatory pathways. Currently, all therapies approved for IBD manipulate the immune system by inhibiting pro-inflammatory mechanisms, such as tumor necrosis factor-α, gut-homing α4β7 integrin, interleukin-12/interleukin-23, and Janus kinases. However, some IBD patients are non-responders to these drugs, which are also associated with serious side effects. Thus, it has been hypothesized that therapies aimed at restoring anti-inflammatory signals, by exploiting the tolerogenic potential of cytokines (interleukin-10, transforming growth factor-β, granulocyte macrophage colony-stimulating factor), immune cells (regulatory T cells, tolerogenic dendritic cells), or mesenchymal stem cells, might offer promising results in terms of clinical efficacy with fewer side effects. In this review, we provide new insights into putative novel treatments aimed at restoring anti-inflammatory signaling pathways in IBD.

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Basal anti-inflammatory responses in cultured endothelial cells exposed to two conjugated linoleic acids

Proceedings of The Nutrition Society ◽

10.1017/s0029665120004310 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Carina Valenzuela ◽

Elizabeth Miles ◽

Philip Calder

Keyword(s):

Inflammatory Responses ◽

Adhesion Assay ◽

Dependent Manner ◽

Relative Expression ◽

Inflammatory Pathways ◽

Expression Of Genes ◽

Low Concentrations ◽

Genes Encoding ◽

Anti Inflammatory ◽

Pre Treatment

AbstractConjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways. Whether low concentrations of CLAs are able to affect basal, unstimulated endothelial cell (EC) responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 and trans-10, cis-12) on basal inflammatory responses by ECs.EA.hy926 cells (HUVEC lineage) were cultured under standard conditions and exposed to CLAs (1 and 10 μM) for 48 hours. MTT assay was performed to determine cell viability; incorporation of FA was confirmed by gas chromatography; inflammatory mediators were assessed by multiplex immunoassay; the relative expression of genes encoding transcription factors and inflammatory cytokines was assessed through real-time PCR and static adhesion assay was used to evaluate monocyte attachment to the EC monolayer.CLAs were incorporated into ECs in a dose-dependent manner. Pre-treatment with CLA9,11 (1 uM) significantly reduced unstimulated, basal concentrations of MCP-1 (p < 0.05), and CLA10,12 at 10 uM had the same effect (p < 0.05). Both CLAs at 10 uM increased the relative expression of NFκβ (p < 0.01 and p < 0.05, respectively), while decreasing the relative expression of PPARα (p < 0.0001), COX-2 (p < 0.0001) and IL-6 (p < 0.0001). In contrast, no effect was observed in the adhesion assay for either CLA.These results suggest that both CLAs at a low concentration have a neutral or modest anti-inflammatory effect in basal conditions, which may influence endothelial function and risk of vascular disease. Interestingly, at these low CLA concentrations some pro-inflammatory genes are upregulated while others are down regulated. This suggests complex effects of CLAs on inflammatory pathways.

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