Euphorbia prostata Exerts Potent Anti-Inflammatory and Anti-Arthritic Activity in Downregulating the Increased Expression of Pro-Inflammatory Cytokines

2020 ◽  
Vol 26 (4) ◽  
pp. 370-378
Author(s):  
Dewi Melani Hariyadi ◽  
Vikram Kumar Sahu
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Joint Destruction ◽  
Immunohistochemical Analysis ◽  
Daily Basis ◽  
Reference Drug ◽  
Macrophage Activity ◽  
Euphorbia Prostrata ◽  
Kg Medium ◽  
Functional Components

Background: Euphorbia prostrata constitutes a herbal medication widely used to cure numerous inflammatory diseases occurring either alone or in conjunction with other herbal formulations. The research conducted was devised with the aim of determining the effect of Euphorbia prostrata hydroalcoholic leaf extract on paw swelling, joint destruction, and the formation of inflammation-producing cytokines in animal models of rheumatoid arthritis. Methods: Hydroalcoholic Euphorbia prostrata extract and a reference drug (indomethacin 3mg/kg), were both administered orally on a daily basis at varying doses; low (50 mg/kg), medium (100 mg/kg), and high (200 mg/kg) for a period of 21 days. Other parameters affecting the functional components of bone include joint diameter measurements and histopathological investigations. Immunohistochemical analysis of Interleukin (IL-1, IL-6) and Nuclear Factor(NF-κB)in ankle joint tissue was performed. Results: The research findings indicated that a significant (p<0.05) dose-dependent reduction in inflammation results from the administering of Euphorbia prostrata at varying doses. A 200mg/kg dose of Euphorbia prostrata with a significance of p<0.001 produced a marked reduction in both inflammation and joint dysfunction. It was concluded, therefore, that such a dose attenuates paw oedema and inflammation, while also reversing bone damage through the inhibition of activated pro-inflammatory mediators and, specifically, NF-κB-mediated production of cytokines. Conclusion: The research presented here concludes that Euphorbia prostrata hydroalcoholic extract can be potentially employed in the treatment and management of rheumatoid arthritis since it reduces symptoms of inflammation, inhibits macrophage activity and modulates IL-1, IL-6 and NF-κB.

scholarly journals Enigma of IL-17 and Th17 Cells in Rheumatoid Arthritis and in Autoimmune Animal Models of Arthritis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Reka Kugyelka ◽  
Zoltan Kohl ◽  
Katalin Olasz ◽  
Katalin Mikecz ◽  
Tibor A. Rauch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Animal Models ◽  
Immune Cells ◽  
Th17 Cells ◽  
Inflammatory Diseases ◽  
Joint Destruction ◽  
Rodent Models ◽  
Immune Functions

Rheumatoid arthritis (RA) is one of the most common autoimmune disorders characterized by the chronic and progressive inflammation of various organs, most notably the synovia of joints leading to joint destruction, a shorter life expectancy, and reduced quality of life. Although we have substantial information about the pathophysiology of the disease with various groups of immune cells and soluble mediators identified to participate in the pathogenesis, several aspects of the altered immune functions and regulation in RA remain controversial. Animal models are especially useful in such scenarios. Recently research focused on IL-17 and IL-17 producing cells in various inflammatory diseases such as in RA and in different rodent models of RA. These studies provided occasionally contradictory results with IL-17 being more prominent in some of the models than in others; the findings of such experimental setups were sometimes inconclusive compared to the human data. The aim of this review is to summarize briefly the recent advancements on the role of IL-17, particularly in the different rodent models of RA.

Immunoregulatory Role of Interleukin-37 in Rheumatoid Arthritis; Relation to Disease Activity and Joint Destruction

2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Destruction

The Role of Synovial Fibroblasts in Mediating Joint Destruction in Rheumatoid Arthritis

2005 ◽  
Vol 11 (5) ◽  
pp. 563-568 ◽  
Author(s):  
Ingmar Meinecke ◽  
Edita Rutkauskaite ◽  
Steffen Gay ◽  
Thomas Pap
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Synovial Fibroblasts

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

scholarly journals Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Scott A. Scarneo ◽  
Liesl S. Eibschutz ◽  
Phillip J. Bendele ◽  
Kelly W. Yang ◽  
Juliane Totzke ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Bone Formation ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Cartilage Damage ◽  
Cytokine Signaling ◽  
Periosteal Bone Formation ◽  
Bone Width

Abstract Objectives To examine the ability of takinib, a selective transforming growth factor beta-activated kinase 1 (TAK1) inhibitor, to reduce the severity of murine type II collagen-induced arthritis (CIA), and to affect function of synovial cells. Methods Following the induction of CIA, mice were treated daily with takinib (50 mg/kg) and clinical scores assessed. Thirty-six days post-CIA induction, histology was performed on various joints of treated and vehicle-treated animals. Inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation were quantified. Furthermore, pharmacokinetics of takinib were evaluated by LC-MS in various tissues. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells were cultured with 10 μM takinib and cytokine secretion analyzed by cytokine/chemokine proteome array. Cytotoxicity of takinib for RA-FLS was measured with 24 to 48 h cultures in the presence or absence of tumor necrosis factor (TNF). Results Here, we show takinib’s ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling. Conclusion Our findings support the hypothesis that TAK1 targeted therapy represents a novel therapeutic axis to treat RA and other inflammatory diseases.

scholarly journals FRI0127 Suppression of radiographic progression after gradual methotrexate tapering in patients with rheumatoid arthritis patients maintaining low disease activity - Prospective multicenter study-

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 645.1-645
Author(s):  
K. Katayama ◽  
K. Yujiro ◽  
T. Okubo ◽  
R. Fukai ◽  
T. Sato ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Destruction ◽  
Reduction Rate ◽  
Bone Destruction ◽  
High Response ◽  
Continuation Rate ◽  
Low Disease Activity ◽  
One Year ◽  
Response Group

Background:Many studies have been reported to reduce/discontinue Biologics in the treatment of rheumatoid arthritis (RA). In contrast, study for tapering methotrexate (MTX) has been limited (1,2).Objectives:We prospectively examined whether bone destruction will progress at 48 weeks after tapering or discontinuing MTX (UMIN000028875).Methods:The subjects were RA patients who have maintained low disease activity or lower for 24 weeks or more in DAS28-CRP after MTX administration. Patients having PDUS Grade 2 or 3 per site by bilateral hand ultrasonography (26 area) were excluded in this study owing to risk for joint destruction. The joint destruction was evaluated by the joint X-ray evaluation by modified total Sharp scoring (mTSS) at 1 year after the start of tapering MTX. Evaluation of clinical disease activities, severe adverse events, the continuation rate during MTX tapering were also evaluated. According to tapering response, prognostic factor for good response for tapering, joint destruction was determined. Predictors for successful tapering MTX and progression of bone destruction were determined. Statistical analysis was performed by t-test or Wilcoxon rank sum test using SAS .13.2 software.Results:The subjects were 79 (16 males, 63 females). Age average 60.9 years, disease duration 4 years 4 months, MTX dose 8.43 mg / w, DAS28-CRP 1.52, DMARDs (24.3%), ACPA 192.7 U / ml (70.5%), RF 55.6 IU / ml (65.4%).MTX was tapered from an average of 8.43 mg / w before study to 5.46 mg / w one year later. In the treatment evaluation, DAS28-CRP increased from 1.52 to 1.84. 89.7% of subjects did not progress joint damage. Other disease activities significantly increased (Table 1). The one-year continuation rate was 78.2%. Since tapering effects were varied widely, we divided patients into three groups; Flared group (N=14, initial MTX dose 8.71mg/w, final MTX dose 8.42mg/w), Low response group (N=31, final MTX reduction rate< 50%, initial MTX dose 8.93mg/w, final MTX dose 6.22mg/w), High response group (N=34, final MTX reduction rate≥ 50%, initial MTX dose 8.5mg/w, final MTX dose 3.15mg/w)(Table 2).Higher RF value at baseline and higher MTX dose at 3M, 6M were predictors of whether a subject was in Low response group or High Response group. Higher RF value and mTSS at baseline and higher MTX dose at 6M were predictors whether a subject was in Flared group or High response group. Lower age was predictor of whether a subject was in Flared group or Low responder group. Finally, mean ΔmTSS /y in Flared group (0.36) was not significantly higher than in low response group (0.07) and in high response group (0.01).Table 1Table 2.Predictors for successful tapering MTX and progression of bone destructionConclusion:Patients with MTX-administered low disease activity and finger joint echo PDUS grade 1 satisfy almost no joint destruction even after MTX reduction. For tapering, predictors may be helpful for maintaining patient’s satisfaction.References:[1]Baker KF, Skelton AJ, Lendrem DW et al. Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study. J. Autoimmunity. 2019;105: 102298.[2]Lillegraven S, Sundlisater N, Aga A et al. Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial. American College of Rheumatology. 2019; Abstract L08.Disclosure of Interests:None declared

scholarly journals POS1180 TREATMENT COMPLIANCE OF PATIENTS WITH RHEUMATOID ARTHRITIS DURING THE FIRST WAVE OF THE SARS-CoV-2/COVID-19 PANDEMIC IN PORTUGAL: RESULTS FROM THE COVID IN RA (COVIDRA) SURVEY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 871.2-871
Author(s):  
F. Araujo ◽  
N. Gonçalves ◽  
A. F. Mourão
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Treatment Compliance ◽  
Web Based ◽  
Symptoms Of Depression ◽  
Immune Mediated ◽  
Attending Physician ◽  
The Impact ◽  
E Mail

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.

Sign in / Sign up

Export Citation Format

Share Document