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

Abstract

Rheumatoid arthritis (RA) as a long-term autoimmune disease is characterized by pain, swelling and joints destruction. The therapeutic efficacy of Guluronic acid (G2013) (patented, DEU: 102016113017.6) was reported in phase I/II clinical trial in RA patients. In this study, we aimed to evaluate the effect of G2013 as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property on genes expression of anti-inflammatory and pro-inflammatory cytokines and their transcription factors in the blood sample of RA patients.
 This study was performed on 12 patients with RA who had an inadequate response to conventional treatments which were disease-modifying anti-rheumatic drugs (DMARDs), NSAID, and biologics. G2013 was administered orally at a dose of 500 mg twice daily for 12 weeks. Before and after the treatment of patients with drug G2013, the peripheral blood mononuclear cells (PBMCs) were isolated for evaluating the gene expression level of interleukin 10 (IL10), interleukin 22 (IL22), interferon γ (IFNγ), and transcription factors specific to the T helper cell lineages, forkhead box P3 (Fox-P3), Aryl hydrocarbon receptor (AHR) and T-box–containing protein expressed in T cells (T-bet) using the real-time PCR method. Since these cytokines have a key role in the progression of RA and disease condition expected induction of IFNγ, AHR, IL22, T-bet, and reduction of IL10, Fox-P3.
 Results indicated a significant reduction in the level of IFNγ, AHR and a significant induction in IL10, Fox-P3 gene expression in comparison with the control group.
 In conclusion; the results of this investigation showed a part of the immunological mechanism of G2013 as a novel anti-inflammatory that could reduce pro-inflammatory cytokine and their transcription factors. Furthermore, it increased the anti-inflammatory cytokine and its transcription factor (clinical trial identifier: IRCT2016092813739N5).

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“…In agreement with previous research, our findings revealed prevalent macroscopic and microscopic indicators of arthritis (Asenso et al 2019 ; Sun et al 2021 ; Shokry et al 2022 ). TNF-α and IL-1β, as well as other pro-inflammatory cytokines produced by activated macrophages and synovial fibroblasts are major inflammatory factors in RA pathogenesis (Bakhtiari et al 2019 ; Dong et al 2020a , b ). Moreover, NLRP3-mediated caspase-1 activation plays a crucial role in osteoarthritis and RA progression ( Guo et al 2018b ; Zu et al 2019 ).…”

An Insight into the Health Benefits of Sodium Alginate and its Derivatives

“…showed that guluronic acid could reduce pro-inflammatory cytokine and their transcription factors in the blood sample of RA patients who received a dose of 500 mg twice daily for 12 weeks. They found that guluronic acid could diminish pro-inflammatory cytokines and their transcription factors and increase the anti-inflammatory cytokine and its associated transcription factor [100]. High production of pro-inflammatory factors is the cause of hyperinflammation in Nonalcoholic Steatohepatitis (NASH).…”

Evaluation of G2013 (α‐L‐guluronic acid) efficacy on PC‐3 cells through inhibiting the expression of inflammatory factors

“…24,25 In several studies, the therapeutic potential of G2013 has been shown for three autoimmune diseases of ankylosing spondylitis, rheumatoid arthritis, and multiple sclerosis. 17,18,22,[26][27][28][29][30] At present, G2013 is in the first and second phases of clinical trials on ankylosing spondylitis (IRCT2016091813739N4) and rheumatoid arthritis (IRCT2016092813739N5), respectively, and in the second phase of a clinical trial on multiple sclerosis (IRCT2017042313739N8). Results of a recent study on breast cancer cell line 4T1 have shown that G2013 can inhibit cancer-related inflammation and has the potential to be used in cancer treatment.…”