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. (2nd January 2020)

• Record Type: Journal Article
• Authors: Khadem Azarian, Shahin; Jafarnezhad-Ansariha, Fahimeh; Nazeri, Sepideh; Azizi, Gholamreza; Aghazadeh, Zahra; Hosseinzadeh, Elham; Mirshafiey, Abbas
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 42:Number 1(2020)
• Page Start: 22
• Page End: 27
• Publication Date: 2020-01-02
• Subjects: G2013 -- guluronic acid -- rheumatoid arthritis -- NSAID -- DMARD; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.1080/08923973.2019.1702053
• Languages: English
• ISSNs: 0892-3973

Abstract

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).