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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

Authors Barati A, Jamshidi AR, Ahmadi H, Aghazadeh Z, Mirshafiey A

Received 4 December 2016

Accepted for publication 15 February 2017

Published 30 March 2017 Volume 2017:11 Pages 1027—1033

DOI https://doi.org/10.2147/DDDT.S129419

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rasika Samarasinghe

Peer reviewer comments 3

Editor who approved publication: Dr Anastasios Lymperopoulos

Anis Barati,1 Ahmad Reza Jamshidi,2,* Hossein Ahmadi,1 Zahra Aghazadeh,1 Abbas Mirshafiey1,*

1Department of Immunology, School of Public Health, 2Iranian Institute for Health Sciences Research, Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

*These authors contributed equally to this work

Abstract: Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-D-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2).

Keywords: M2000, IL17, RORγt, rheumatoid arthritis, inflammation, immunosuppressive

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