scholarly journals Flavonoids: Nutraceuticals for Rheumatic Diseases via Targeting of Inflammasome Activation

2021 ◽  
Vol 22 (2) ◽  
pp. 488
Author(s):  
Young-Su Yi
Keyword(s):  
Rheumatic Diseases ◽  
Fruits And Vegetables ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Cellular Damage ◽  
Inflammatory Rheumatic Diseases ◽  
Inflammasome Activation ◽  
Central Feature ◽  
Inflammatory Protein ◽  
Anti Inflammatory

Inflammation, an innate immune response that prevents cellular damage caused by pathogens, consists of two successive mechanisms, namely priming and triggering. While priming is an inflammation-preparation step, triggering is an inflammation-activation step, and the central feature of triggering is the activation of inflammasomes and intracellular inflammatory protein complexes. Flavonoids are natural phenolic compounds predominantly present in plants, fruits, and vegetables and are known to possess strong anti-inflammatory activities. The anti-inflammatory activity of flavonoids has long been demonstrated, with the main focus on the priming mechanisms, while increasing numbers of recent studies have redirected the research focus on the triggering step, and studies have reported that flavonoids inhibit inflammatory responses and diseases by targeting inflammasome activation. Rheumatic diseases are systemic inflammatory and autoimmune diseases that primarily affect joints and connective tissues, and they are associated with numerous deleterious effects. Here, we discuss the emerging literature on the ameliorative role of flavonoids targeting inflammasome activation in inflammatory rheumatic diseases.

scholarly journals Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses

2021 ◽  
Author(s):  
Mamdooh Ghoneum ◽  
Mohamed S. A. El-Gerbed
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Biological Effects ◽  
Cellular Damage ◽  
Male Rats ◽  
Antioxidant Enzyme Activities ◽  
Oxidative Stress Biomarkers ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Liver Tissues

Abstract Purpose Methotrexate (MTX) induces hepatotoxicity, limiting its clinical efficacy as a widely known chemotherapy drug. In the current study, we examined the protective effect of human placenta extract (HPE) against MTX-induced liver damage in rats, as well as its ability to regulate antioxidative and anti-inflammatory liver responses. Methods Male rats were orally administered MTX at a daily dose of 5 mg/kg-body-weight in the presence or absence of HPE (10.08 mg/kg) for 2 weeks. We measured the biological effects of MTX and HPE on the levels of liver enzymes, lipid profile, lipid peroxidation, oxidative stress biomarkers, and cytokines [tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)]. In addition, histological examination and histopathological scoring of liver tissues were performed. Results MTX-treated rats showed significantly increased (p < 0.001) liver enzyme levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, total cholesterol, and triglyceride levels. However, HPE supplementation in MTX-treated rats significantly decreased (p < 0.001) these elevated levels. HPE supplementation also significantly reduced the oxidative stress biomarker malondialdehyde (MDA), reversed the reduction in glutathione (GSH), and markedly increased the antioxidant enzyme activities of catalase (CAT) and superoxide dismutase (SOD) in the livers of MTX-treated rats. Furthermore, HPE supplementation significantly decreased the MTX-elevated levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-10. Histopathological examinations showed that MTX produced severe cellular damage and inflammatory lesions in liver tissues, while treatment with HPE improved hepatic histologic architecture. Conclusion HPE has the ability to ameliorate methotrexate-induced liver injury in rats by mechanisms that include boosting antioxidative responses and down-regulating MDA and pro-inflammatory cytokine production.

scholarly journals NLRP3 inflammasome in endothelial dysfunction

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Baochen Bai ◽  
Yanyan Yang ◽  
Qi Wang ◽  
Min Li ◽  
Chao Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Cell Damage ◽  
Inflammasome Activation ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Clinical Drugs

Abstract Inflammasomes are a class of cytosolic protein complexes. They act as cytosolic innate immune signal receptors to sense pathogens and initiate inflammatory responses under physiological and pathological conditions. The NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18, which are mediated by caspase-1, and secretes mature forms of these mediators from cells to promote the further inflammatory process and oxidative stress. Simultaneously, cells undergo pro-inflammatory programmed cell death, termed pyroptosis. The danger signals for activating NLRP3 inflammasome are very extensive, especially reactive oxygen species (ROS), which act as an intermediate trigger to activate NLRP3 inflammasome, exacerbating subsequent inflammatory cascades and cell damage. Vascular endothelium at the site of inflammation is actively involved in the regulation of inflammation progression with important implications for cardiovascular homeostasis as a dynamically adaptable interface. Endothelial dysfunction is a hallmark and predictor for cardiovascular ailments or adverse cardiovascular events, such as coronary artery disease, diabetes mellitus, hypertension, and hypercholesterolemia. The loss of proper endothelial function may lead to tissue swelling, chronic inflammation, and the formation of thrombi. As such, elimination of endothelial cell inflammation or activation is of clinical relevance. In this review, we provided a comprehensive perspective on the pivotal role of NLRP3 inflammasome activation in aggravating oxidative stress and endothelial dysfunction and the possible underlying mechanisms. Furthermore, we highlighted the contribution of noncoding RNAs to NLRP3 inflammasome activation-associated endothelial dysfunction, and outlined potential clinical drugs targeting NLRP3 inflammasome involved in endothelial dysfunction. Collectively, this summary provides recent developments and perspectives on how NLRP3 inflammasome interferes with endothelial dysfunction and the potential research value of NLRP3 inflammasome as a potential mediator of endothelial dysfunction.

scholarly journals A Review on Pharmacological Activities of Lupeol and its Triterpene Derivatives

2020 ◽  
Vol 10 (5) ◽  
pp. 325-332
Author(s):  
Nitika Sharma ◽  
Priyankul Palia ◽  
Amit Chaudhary ◽  
, Shalini ◽  
Kritika Verma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Free Radical ◽  
Cancer Cells ◽  
Fruits And Vegetables ◽  
Inflammatory Responses ◽  
Pharmacological Activities ◽  
Pentacyclic Triterpenoid ◽  
Naturally Occurring ◽  
Lupeol Linoleate ◽  
Anti Inflammatory

Lupeol is a pentacyclic triterpenoid commonly distributed in the plant kingdom and is found in edible fruits and vegetables. It is a naturally occurring triterpene that is used to reduce the inflammatory responses and also have immunomodulating properties. Lupeol and its derivatives have a great potential to act as an anti- inflammatory, anti-microbial, anti-proliferative, anti-invasive, anti-angiogenic, anti-protozoal, and cholesterol-lowering agent. Various studies have shown that anti-inflammatory activity of lupeol through the modulation of p-38 pathways inhibits neuroinflammation in the cerebellum and induces neuroprotection. It has been also found effective on lung cancer (i.e A427 cancer cells and normal MRC-5 cells). Observation of inhibiting the growth of lung cancer cells is checked by MTT assay. Lupeol and its ester lupeol linoleate have been used to reduce the levels of hypercholesterolemia in the rats and decrease the activities of such enzymes namely Na+, K+-ATPase, Ca2+-ATPase, and Mg2+. Lupeol also decreases the levels of calcium-oxalate and has cytoprotective action against free-radical-induced damage and also decreases the level of cadmium in the kidney. Keywords: Lupeol, anti- inflammatory, anti-protozoal, triterpenoids

scholarly journals Decreased Anti-Inflammatory Responses to Vitamin D in Neonatal Neutrophils

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Daniel Hirsch ◽  
Faith E. Archer ◽  
Meera Joshi-Kale ◽  
Anna M. Vetrano ◽  
Barry Weinberger
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Inflammatory Responses ◽  
Vdr Gene ◽  
Induced Expression ◽  
Hydroxyvitamin D ◽  
Inflammatory Protein ◽  
25 Hydroxyvitamin D ◽  
Anti Inflammatory ◽  
Macrophage Inflammatory Protein

Neutrophil activity is prolonged in newborns, suggesting decreased exposure and/or responses to immunosuppressive modulators, such as 1,25-hydroxyvitamin D3(1,25-vit D3). We hypothesized that 1,25-vit D3suppresses neutrophil activation and that this response is impaired in newborns. Consistent with this, 1,25-vit D3decreased LPS-induced expression of macrophage inflammatory protein-1βand VEGF in adult, but not neonatal, neutrophils. Expression of vitamin D receptor (VDR) and 25-hydroxyvitamin D3-1α-hydroxylase was reduced in neonatal, relative to adult neutrophils. Moreover, 1,25-vit D3induced VDR gene expression in activated adult, but not neonatal, neutrophils. 1,25-vit D3also suppressed expression of cyclooxygenase-2 and induced expression of 5-lipoxygenase in LPS-exposed adult neutrophils, while neonatal cells were not affected. 1,25-vit D3had no effect on respiratory burst in either adult or neonatal cells. Anti-inflammatory activity of vitamin D is impaired in neonatal neutrophils, and this may be due to decreased expression of VDR and 1α-hydroxylase. Insensitivity to 1,25-vit D3may contribute to chronic inflammation in neonates.

scholarly journals POS1198 THE ROLE OF SOCS3 IN COLCHICINE ANTI-INFLAMMATORY EFFECT ON COVID-19 INFECTION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 881-881
Author(s):  
M. Y. Hachim ◽  
F. Alqutami ◽  
S. Hannawi
Keyword(s):  
Gene Expression ◽  
Venous Thromboembolism ◽  
Rheumatic Diseases ◽  
Meta Analysis ◽  
Cytokine Signaling ◽  
Inflammatory Rheumatic Diseases ◽  
Online Tool ◽  
Gene Sets ◽  
Increased Risk ◽  
Anti Inflammatory

Background:In the fight against COVID-19, the use of an old anti-gout agent which is inexpensive and easily administered (1). A meta-analysis suggests a definite benefit with the addition of colchicine in patients with COVID-19(2). It was suggested that colchicine can have efficacy for hospitalized patients with a severe course of COVID-19 and concurrent inflammatory rheumatic diseases who have a higher risk of venous thromboembolism (3). On the other hand, some reports suggested that colchicine is associated with an increased risk of infections (4). Currently, there are nine clinical trials using colchicine for COVID-19(5), nevertheless, the exact mechanism of action is not well understood.Objectives:Using publicly available transcriptomic data profiling human cells’ response to colchicine to identify core differentially expressed genes (DEGs) then examine the dynamics of the identified DEGs in different datasets of COVID-19 transcriptomics databases to suggest the possible mechanisms of action on the molecular level.Methods:Gene Expression Omnibus was searched for human samples treated with colchicine compared to controls. GSE4090 dataset was identified where global gene expression of HUVEC (human umbilical vein endothelial cell line) cells exposed to various concentrations of colchicine (n=9) compared to controls (n=7). We reanalyzed this datset using GEO2R online tool to identify DEGs. The identified DEGs were searched in SARS-CoV-2 transcriptome datasets using metascape online tool to identify gene sets were the DEGs identified showed significant similarity.Results:Fifty DEGs were identified in response to colchicine no matter what the concentration is used, (Figure 1A). Two gene sets (COVID323, RNA_Wilk_CD4+T-cells_patient-C2_Up [peripheral immune cells] and COVID008, RNA_Blanco-Melo_A549_Up[lung epithelial cells]) showed significant enrichment of the identified DEGs, (Figure 1B). SOCS3, ZC3H12C, CD55, GLIPR1, BACH1, PHLDA1, JUNB, NFKBIZ, and MYLIP were the shared genes between the identified DEGs, and the two gene sets with top enriched terms related to important immune-related pathways like IL-6, chemotaxis, leukocytes migration, cytokine release, and response to glucocorticoid, (Figure 1C). Only Suppressor of cytokine signaling 3 (SOCS3) was shared in the three datasets. SOCS3 expression was significantly downregulated in the HUVEC cells exposed to colchicine, (Figure 1D). Next, the normalized gene expression of SOCS3 from whole blood of 62 COVID-19 patients was compared to that of 24 healthy controls using (GSE15264) showed significant upregulation of SOCS3 in the blood of CVOID-19 patients indicating its role in COVID-19, (Figure 1E).Conclusion:Our reanalysis showed that the possible beneficial effect of colchicine in COVID-19 patients might be through its direct effect on SOCS3 which is specifically upregulated in COVID-19 by IL6 and interferon (IFN)-gamma.References:[1]Reyes AZ, Hu KA, Teperman J, Wampler Muskardin TL, Tardif J-C, Shah B, et al. Anti-inflammatory therapy for COVID-19 infection: the case for colchicine. Annals of the Rheumatic Diseases. 2020:annrheumdis-2020-219174.[2]Vrachatis DA, Giannopoulos GV, Giotaki SG, Raisakis K, Kossyvakis C, Iliodromitis KE, et al. Impact of colchicine on mortality in patients with COVID-19. A meta-analysis. Hellenic Journal of Cardiology. 2021.[3]Kow CS, Hasan SS. Colchicine as an adjunct to heparin for prophylaxis of venous thromboembolism in patients with COVID-19. Rheumatol Int. 2021:1-2.[4]McEwan T, Robinson PC. A systematic review of the infectious complications of colchicine and the use of colchicine to treat infections. Semin Arthritis Rheum. 2020;51(1):101-12.[5]Montealegre-Gómez G, Garavito E, Gómez-López A, Rojas-Villarraga A, Parra-Medina R. Colchicine: A potential therapeutic tool against COVID-19. Experience of 5 patients. Reumatología Clínica. 2020.Disclosure of Interests:None declared.

scholarly journals Royal Jelly InhibitsPseudomonas aeruginosaAdherence and Reduces Excessive Inflammatory Responses in Human Epithelial Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Heni Susilowati ◽  
Keiji Murakami ◽  
Hiromichi Yumoto ◽  
Takashi Amoh ◽  
Kouji Hirao ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Respiratory Infection ◽  
Royal Jelly ◽  
Inflammatory Responses ◽  
Inhibitory Effect ◽  
Abiotic Surface ◽  
Inflammatory Protein ◽  
Traditional Remedy ◽  
Antibacterial Assay ◽  
Anti Inflammatory

Pseudomonas aeruginosais a Gram-negative bacterium and causes respiratory infection especially in elderly patients. Royal jelly has been used worldwide as a traditional remedy and as a nutrient; however, the effect againstP. aeruginosais unclear. The aim of this study was to analyze antibacterial, antiadherent, and anti-inflammatory effects of royal jelly againstP. aeruginosa. Wild-type strain PAO1 and clinical isolates ofP. aeruginosawere used for antibacterial assay and antiadherent assay to abiotic surface and epithelial cells, which are pharynx (Detroit 562) and lung (NCI-H292) epithelial cells. In anti-inflammatory assay, epithelial cells were pretreated with royal jelly before bacterial exposure to investigate its inhibitory effect on interleukin (IL-8) and macrophage inflammatory protein-3α/CCL20 overproduction. Although royal jelly did not have antibacterial activity at concentration of 50% w/v, antiadherent activity was confirmed on the abiotic surface and epithelial cells under concentration of 25%. Pretreatment with royal jelly significantly inhibited overproduction of IL-8 and CCL20 from both cells. These results demonstrated that royal jelly inhibitsP. aeruginosaadherence and protects epithelial cells from excessive inflammatory responses againstP. aeruginosainfection. Our findings suggested that royal jelly may be a useful supplement as complementary and alternative medicine for preventing respiratory infection caused byP. aeruginosa.

scholarly journals STW1 and Its Versatile Pharmacological and Clinical Effects in Rheumatic Disorders: A Comprehensive Report

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Karl-Josef Gundermann ◽  
Jürgen Müller ◽  
Karin Kraft
Keyword(s):  
Rheumatic Diseases ◽  
Safety Profile ◽  
Comparable Efficacy ◽  
Inflammatory Rheumatic Diseases ◽  
Clinical Effects ◽  
Double Blind ◽  
Solidago Virgaurea ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The Individual

Aim. To review the published and unpublished experimental and clinical studies about the efficacy and tolerability of STW1 and to compare the results to the efficacy and tolerability of investigated NSAIDs in parallel. Content. STW1 (Phytodolor®) contains a fixed combination of extracts from aspen leaves and bark (Populus tremula), common ash bark (Fraxinus excelsior), and goldenrod herb (Solidago virgaurea). It belongs to the group of anti-inflammatory and antirheumatic drugs, and it is authorized for the treatment of painful disorders of degenerative and inflammatory rheumatic diseases. The individual components have complementary effects. Its multifocal mode of action includes antiphlogistic, analgesic, antiexudative, antioxidative, antipyretic, and antiproliferative properties. The effects of both STW1 and its components have been verified in comprehensive pharmacological investigations. Open and randomized, placebo- and verum-controlled, and single-blind (sb) or double-blind (db) clinical trials, performed in different subtypes of rheumatic diseases confirm the pharmacological evidence. Its efficacy is comparable to a range of standard nonsteroidal anti-inflammatory drugs (NSAIDs) studied in parallel, but it has a superior safety profile. Conclusion. STW1 is a reasonable alternative to NSAIDs with comparable efficacy and a superior safety profile. It is also suitable to reduce the intake of NSAIDs.

scholarly journals Cardiovascular safety of non-steroidal anti-inflammatory drugs in chronic inflammatory rheumatic diseases

2018 ◽  
Vol 90 (8) ◽  
pp. 101-106 ◽  
Author(s):  
B V Zavodovsky ◽  
L E Sivordova
Keyword(s):  
Side Effects ◽  
Rheumatic Diseases ◽  
Molecular Mechanisms ◽  
Inflammatory Rheumatic Diseases ◽  
Cardiovascular Safety ◽  
Cardiovascular Side Effects ◽  
Cardiovascular Morbidity And Mortality ◽  
Negative Effect ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Rheumatic diseases (RD), such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, vasculitis, gout are associated with increase in cardiovascular morbidity and mortality. The main causes of increased cardiovascular risk are inflammatory heart and vascular lesions, accelerated progression of atherosclerosis and side effects of drug therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in clinical practice and are on the list of the most prescribed medications. It is known that NSAIDs have a negative effect on the cardiovascular system (CVS). However NSAIDs may decrease the intensity of inflammation, which is an independent risk risk factor for CVS pathology. Therefore in patients with RD it is theoretically possible to reduce the severity of cardiovascular side effects when using NSAIDs. The article discusses the issues of NSAID’s cardiovascular safety, the molecular mechanisms underlying the negative effect of them on CVS, critically evaluated the results of main studies concerning the cardiovascular safety of NSAIDs in chronic inflammatory diseases.

scholarly journals Editorial of Special Issue “Regulatory Roles of Inflammasomes in Human Diseases”

2021 ◽  
Vol 22 (6) ◽  
pp. 3008
Author(s):  
Young-Su Yi ◽  
Miyong Yun
Keyword(s):  
Drug Targets ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
The Body ◽  
Human Diseases ◽  
Inflammasome Activation ◽  
Special Issue ◽  
Intracellular Protein ◽  
Inflammatory Molecules ◽  
Pro Inflammatory Cytokines

Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering (activation step). The key feature of the triggering step is the activation of inflammasomes that are intracellular protein complexes consisting of pattern recognition receptors and inflammatory molecules. Inflammasomes are activated in response to various ligands, leading to the caspase-1-mediated maturation and secretion of pro-inflammatory cytokines, IL-1β and IL-18 and the gasdermin D-mediated pyroptosis, an inflammatory form of cell death. Previous studies have demonstrated that inflammasome activation is a key determinant of inflammatory responses and many human diseases; therefore, inflammasomes have been attracted much attention as critical drug targets to prevent and treat various human diseases.

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