Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Effects of Guluronic Acid, As a New Nsaid With Immunomodulatory Properties on Il-17, Rorγt, Il-4 and Gata-3 Gene Expression in Rheumatoid Arthritis Patients Publisher Pubmed



Khadem Azarian S1, 2 ; Jafarnezhadansariha F1 ; Nazeri S1 ; Azizi G3 ; Aghazadeh Z1 ; Hosseinzadeh E4 ; Mirshafiey A1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  3. 3. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  4. 4. Department of Molecular Imaging, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

Source: Immunopharmacology and Immunotoxicology Published:2020


Abstract

Aim: Rheumatoid arthritis (RA) is a prevalent inflammatory, autoimmune diseases characterized by inflammation and destruction of joints. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can have modulatory interference in disease process. In this study, the effect of Guluronic Acid (G2013) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunomodulatory effects was evaluated on IL-17, RORγt, IL-4 and GATA-3 gene expression in RA patients. Methods: Fourteen patients with RA who had an inadequate response to conventional treatments were included in this clinical trial. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. G2013 was administered orally at dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the gene expression levels of IL-4, GATA-3, IL-17 and RORγt. Results: Primary and secondary efficacy endpoints and Disease Activity Score (DAS) 28 showed an improvement after 12 weeks of treatment. G2013 has a potent efficacy on gene expression of these molecules, so that it could decrease IL-17 and RORγt levels and increase IL-4 and GATA-3 levels after 12 weeks of treatment. Reduction of IL-17 was statistically non-significant whereas for its transcription factor (RORγt) was statistically significant. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. Conclusion: G2013 as a natural novel drug showed a significant increase on IL-4 and GATA-3 and a significant decrease on RORγt gene expression after 12 weeks oral administration of this drug in RA patients. (Clinical trial identifier: IRCT2016092813739N5). © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
Related Docs
View other Related Docs
1. Effects of Β-D-Mannuronic Acid, As a Novel Non-Steroidal Anti-Inflammatory Medication Within Immunosuppressive Properties, on Il17, Rorγt, Il4 and Gata3 Gene Expressions in Rheumatoid Arthritis Patients, Drug Design# Development and Therapy (2017)
2. A Randomized Clinical Trial for the Assessment of the Efficacy and Safety of Guluronic Acid (G2013) in Patients With Rheumatoid Arthritis, Immunopharmacology and Immunotoxicology (2019)
3. Evaluation of the Oral Administration of Α-L-Guluronic Acid on Cox-1 and Cox-2 Gene Expression Profile in Ankylosing Spondylitis Patients, Drug Development Research (2021)
4. Assessment of Immunological Profile in Ankylosing Spondylitis Patients Following a Clinical Trial With Guluronic Acid (G2013), As a New Nsaid With Immunomodulatory Properties, Immunologic Research (2019)
5. Anti-Diabetic and Angio-Protective Effect of Guluronic Acid (G2013) As a New Nonsteroidal Anti-Inflammatory Drug in the Experimental Model of Diabetes, Endocrine# Metabolic and Immune Disorders - Drug Targets (2020)
6. Evaluation of G2013 (Α-L-Guluronic Acid) Efficacy on Pc-3 Cells Through Inhibiting the Expression of Inflammatory Factors, Clinical and Experimental Pharmacology and Physiology (2022)
7. The Application of G2013 (Α-L-Guluronic Acid) As an Anti-Inflammatory Drug Candidate in Treatment of Disease, Journal of Isfahan Medical School (2021)
8. The Open, Randomized, Positive Control Clinical Trial of Guluronic Acid (G2013) on Sars-Cov-2 Patients, Current Drug Discovery Technologies (2023)
Experts (# of related papers)
View all Related Experts
Ahmad Reza Jamshidi (10)
Mahdi Mahmoudi (8)
Other Related Docs
9. Implications of the Noncoding Rnas in Rheumatoid Arthritis Pathogenesis, Journal of Cellular Physiology (2018)
10. A Phase Iii, Randomized, Two-Armed, Double-Blind, Parallel, Active Controlled, and Non-Inferiority Clinical Trial to Compare Efficacy and Safety of Biosimilar Adalimumab (Cinnora®) to the Reference Product (Humira®) in Patients With Active Rheumatoid Arthritis, Arthritis Research and Therapy (2017)
11. Evaluation of the Acute and 28-Day Sub-Acute Intravenous Toxicity of Α-L-Guluronic Acid (Alg; G2013) in Mice, Drug and Chemical Toxicology (2022)
12. The Potent Inhibitory Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property on Anti-Cyclic Citrullinated Peptide Antibodies, Rheumatoid Factor and Antidsdna Antibodies in Patients With Rheumatoid Arthritis, Current Drug Discovery Technologies (2017)
13. The Evaluation of Safety Property and Apoptotic Efficacy of Α-L-Guluronic Acid (G2013), As a Novel Nsaid, Under in Vitro Examination on L929 and Hepatocellular Carcinoma Cell Lines, Recent Advances in Inflammation and Allergy Drug Discovery (2021)
14. International Multicenter Randomized, Placebo-Controlled Phase Iii Clinical Trial of Β-D-Mannuronic Acid in Rheumatoid Arthritis Patients, Inflammopharmacology (2019)
15. Pivotal Cytokines and Their Transcription Factors Are the Targets of Guluronic Acid (G2013) for Inhibiting the Immunopathogenesis Process of Multiple Sclerosis, Drug Development Research (2020)
16. The Effects of Guluronic Acid (G2013), a New Emerging Treatment, on Inflammatory Factors in Nonalcoholic Steatohepatitis Patients Under in Vitro Conditions, Immunopharmacology and Immunotoxicology (2021)
17. Role of Fibroblast Activation Protein Alpha in Fibroblast-Like Synoviocytes of Rheumatoid Arthritis, Iranian Journal of Allergy# Asthma and Immunology (2021)
18. Effect of Guluronic Acid (G2013), As a New Anti-Inflammatory Drug on Gene Expression of Pro-Inflammatory and Anti-Inflammatory Cytokines and Their Transcription Factors in Rheumatoid Arthritis Patients, Iranian Journal of Allergy# Asthma and Immunology (2019)
19. Anti‐Inflammatory and Anti‐Tumor Effects of Α-L-Guluronic Acid (G2013) on Cancer-Related Inflammation in a Murine Breast Cancer Model, Biomedicine and Pharmacotherapy (2018)
20. Targeting of Circulating Th17 Cells by Β-D-Mannuronic Acid (M2000) As a Novel Medication in Patients With Rheumatoid Arthritis, Inflammopharmacology (2018)
21. Evaluation of the Effect of Α-L-Guluronic Acid (G2013) on Cox-1, Cox-2 Activity and Gene Expression for Introducing This Drug As a Novel Nsaid With Immunomodulatory Property, Recent Patents on Inflammation and Allergy Drug Discovery (2018)
22. Effects of Guluronic Acid (G2013) on Ship1, Socs1 Induction and Related Molecules in Tlr4 Signaling Pathway, International Immunopharmacology (2018)
23. A Phase I/Ii Randomized, Controlled, Clinical Trial for Assessment of the Efficacy and Safety of Β-D-Mannuronic Acid in Rheumatoid Arthritis Patients, Inflammopharmacology (2018)
24. Effects of Guluronic Acid (G2013) on Gene Expression of Tlr2, Tlr4, Myd88, Tnf-Α and Cd52 in Multiple Sclerosis Under in Vitro Conditions, Immunopharmacology and Immunotoxicology (2019)
25. The Safety and Efficacy of Guluronic Acid (G2013) in Ankylosing Spondylitis: A Randomized Controlled Parallel Clinical Trial, Pharmacological Reports (2019)
26. Immunotherapeutic Effects of Β-D Mannuronic Acid on Il-4, Gata3, Il-17 and Rorc Gene Expression in the Pbmc of Patients With Inflammatory Bowel Diseases, Iranian Journal of Allergy# Asthma and Immunology (2018)
27. Immunomodulatory Effects of M2000 (Β-D-Mannuronic Acid) on Tnf-Α, Il-17 and Foxp3 Gene Expression in Patients With Inflammatory Bowel Disease, International Immunopharmacology (2017)
28. An in Vitro Evaluation of Anti-Aging Effect of Guluronic Acid (G2013) Based on Enzymatic Oxidative Stress Gene Expression Using Healthy Individuals Pbmcs, Biomedicine and Pharmacotherapy (2017)
29. Dysregulated Mirnas Network in the Critical Covid-19: An Important Clue for Uncontrolled Immunothrombosis/Thromboinflammation, International Immunopharmacology (2022)
30. The Expression of Gas5, Thril, and Rmrp Lncrnas Is Increased in T Cells of Patients With Rheumatoid Arthritis, Clinical Rheumatology (2019)
31. Association of the Genetic Polymorphisms in Inhibiting and Activating Molecules of Immune System With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis, Journal of Research in Medical Sciences (2021)
32. Microrna-211-5P Overexpression Effect on Endoplasmic Reticulum Stress and Apoptotic Genes in Fibroblast-Like Synoviocytes of Rheumatoid Arthritis, Iranian Journal of Allergy# Asthma and Immunology (2022)
33. Antagonistic Property of G2013 (Α-L-Guluronic Acid) on Gene Expression of Myd88, Tollip, and Nf-Κb in Hek293 Tlr2 and Hek293 Tlr4, Endocrine# Metabolic and Immune Disorders - Drug Targets (2019)
34. Lipid Profile Changes in Rheumatoid Arthritis Patients: Investigation of Different Affecting Factors, Acta Medica Iranica (2018)
35. Immunomodulatory Effect of G2013 (Α-L-Guluronic Acid) on the Tlr2 and Tlr4 in Human Mononuclear Cells, Current Drug Discovery Technologies (2018)
36. A Systems Biology Approach for Mirna-Mrna Expression Patterns Analysis in Rheumatoid Arthritis, Combinatorial Chemistry and High Throughput Screening (2021)
37. The Effects of G2013 (Α-L-Guluronic Acid) in a Pentylenetetrazole-Induced Kindling Animal Model of Epilepsy, Innovations in Clinical Neuroscience (2020)
38. The Immunomodulatory Role of G2013 (Α-L-Guluronic Acid) on the Expression of Tlr2 and Tlr4 in Ht29 Cell Line, Current Drug Discovery Technologies (2019)