Anti-aging effects of M2000 (β-D-mannuronic acid) as a novel immunosuppressive drug on the enzymatic and non-enzymatic oxidative stress parameters in an experimental model

Abstract

Our data showed the anti-aging property of M2000 as a novel designed non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property on various oxidative stress determinants.

Toll-Like Receptor 2 Signaling and Current Approaches for Therapeutic Modulation in Synucleinopathies

“…β-D-mannuronic acid (M2000) and its analog α-l-guluronic acid (G2013) are novel non-steroidal anti-inflammatory drugs (NSAIDs) currently being studied. In relation to oxidative stress, M2000 and G2013 non-significantly increase regulatory enzymes related to oxidative stress, but investigation of these two NSAIDs should not be immediately abandoned (Afraei et al, 2015 ; Mirshafiey et al, 2016 ; Hosseini et al, 2017 ). The mode of action for M2000 has been postulated as both a TLR2/TLR4 antagonist (Aletaha et al, 2017 ) and a miR-155 inhibitor (Pourgholi et al, 2017 ).…”

The Inhibitory Role of M2000 (β-D-Mannuronic Acid) on Expression of Toll-like Receptor 2 and 4 in HT29 Cell Line

“…According to the previous studies, the immunosuppressive effects of M2000 were found in animal models and cell lines [21-24, 90]; Also, anti-oxidant property of M2000 and its monomer, G2013 has been proven in animal models [25, 32]. Recently, the results of a clinical trial showed that M2000 has an inhibitory effect on Anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP), Rheumatoid Factor (RF), anti-double strand DNA (anti-dsDNA) and acute phase reactants in RA patients [91].…”

“…We know that oxidative stress damages the mucosal layer of intestines, leading to bacterial invasion, and IBD development [6]. Therefore, due to the capacity of M2000 in suppressing TLR2 and TLR4 and its role in oxidative stress reduction M2000 [25, 32] we anticipate a potent capacity of M2000 for preventing IBD. More comprehensive in vitro and in vivo studies are needed to recognize the molecular mechanism of M2000 and also its probable side effects.…”

“…Recently Mirshafiey et al . indicated the satisfactory effect of M2000 on several antioxidant enzymes and their gene expression, including SOD2, CAT, GPX1, and GST [25]. Recently, the efficacy and safety of M2000 were approved in clinical trial Phase I/II on RA (IRCT2014011213739N2) and clinical trial Phase I/II on AS (IRCT2013062213739N1) [26, 27].…”

“…Due to the capacity of M2000 in suppressing some molecules involved in TLRs signaling [28-31] and reducing oxidative stress [25, 32], we hypothesize that this molecule may have a potential role in decreasing inflammatory responses in IBD. The aim of this study was to evaluate the cytotoxicity of M2000 and to determine whether M2000 is able to inhibit the gene expression of TLR2 and TLR4 in HT29 cells.…”