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  • The effects of beta-d-mannuronic acid (M2000), as a novel NSAID, on COX1 and COX2 activities and gene expression in ankylosing spondylitis patients and the murine monocyte/macrophage, J774 cell line

    Author(s)
    Jafarnezhad-Ansariha, Fahimeh
    Yekaninejad, Mir Saeed
    Jamshidi, Ahmad-reza
    Mansouri, Reza
    Vojdanian, Mahdi
    Mahmoudi, Mahdi
    Fattahi, Mohammad Javad
    Hashemi, Seyed Naser
    Rehm, Bernd HA
    Matsuo, Hidenori
    Esposito, Emanuela
    Cuzzocrea, Salvatore
    Mirshafiey, Abbas
    Griffith University Author(s)
    Rehm, Bernd
    Year published
    2018
    Metadata
    Show full item record
    Abstract
    Ankylosing spondylitis (AS) is a debilitating chronic inflammatory disease with genetic predisposition, which is characterized by the involvement of spine and sacroiliac joints. Due to the relatively unsuccessful treatments, we designed β-d-mannuronic (M2000) with the beneficial effects in various experimental models as a novel non-steroidal anti-inflammatory drug (NSAID). The aims of our present study were: first, to compare the therapeutic effects of M2000, as a novel designed NSAID, with naproxen and placebo in Iranian patients with AS during 12 weeks; second, to evaluate the effect of M2000 on gene expression of ...
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    Ankylosing spondylitis (AS) is a debilitating chronic inflammatory disease with genetic predisposition, which is characterized by the involvement of spine and sacroiliac joints. Due to the relatively unsuccessful treatments, we designed β-d-mannuronic (M2000) with the beneficial effects in various experimental models as a novel non-steroidal anti-inflammatory drug (NSAID). The aims of our present study were: first, to compare the therapeutic effects of M2000, as a novel designed NSAID, with naproxen and placebo in Iranian patients with AS during 12 weeks; second, to evaluate the effect of M2000 on gene expression of cyclooxygenase enzyme (COX-1/COX-2), a key enzyme in the initiation of inflammatory pathways in AS patients; and third, to assess the activity of COX-1 and COX-2 enzymes in the presence/absence of M2000 at the different doses in the murine macrophage, J774 cell line. This was a sub-study of phase II, randomized, placebo-controlled trial with three treatment arms: M2000, naproxen, and placebo. The outcome measures were the mean changes from baseline to week 12. The gene expression was assessed by real-time PCR. The COX-1 and COX-2 activities were evaluated by ELISA in J774 cell line induced by LPS and arachidonic acid (AA). Our findings demonstrated that M2000 had beneficial therapeutic effects on pain, stiffness, and inflammation, whereas no adverse effects were observed following the use of M2000 after 12 weeks. The analysis of gene expression showed that M2000 could effectively reduce the expression levels of COX-1 and COX-2 in comparison with untreated patients. In addition, the enzymatic activities in the presence of M2000 were significantly less than LPS- and AA-treated groups. Our results indicate that M2000, as a novel designed NSAID with immunosuppressive properties, can be considered as one of the therapeutic options for the treatment of inflammatory diseases without adverse events.
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    Journal Title
    Inflammopharmacology
    Volume
    26
    DOI
    https://doi.org/10.1007/s10787-017-0386-4
    Note
    This publication has been entered into Griffith Research Online as an Advanced Online Version.
    Subject
    Pharmacology and pharmaceutical sciences
    Pharmacology and pharmaceutical sciences not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/370294
    Collection
    • Journal articles

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