ß-D-Mannuronic Acid (M2000) as a Landmark in Pharmacology.

OBJECTIVES: The goal of this article is to retrace the studies of ß-D-Mannuronic Acid (M2000) as a new immunosuppressive drug with non-steroidal anti-inflammatory drugs (NSAIDs) property in miscellaneous aspects including in vitro, in vivo examinations, clinical trials and related to clinical trials studies. Our goal is to compare the effect of this drug with other similar drugs through varied researches and to follow tolerability, biocompatibility, potency, safety, and efficacy of this medication in different studies, as well as to evaluate its therapeutic effectiveness in various diseases. MATERIALS AND METHODS: Different methods were applied in the studies of ß-D-Mannuronic Acid under in vitro, in vivo examinations, and clinical trials phase I, II and III and related investigations to these clinical trials using different techniques showing the efficacy of this medication in the treatment of various diseases. RESULTS: The administration of ß -D-Mannuronic Acid showed the greatest tolerability and biocompatibility compared to diclofenac, piroxicam, and dexamethasone without or very low side effects. The drug has shown a punchy effect on many molecules which participate either in physiologic or in pathogenic activities in animal models and human. This new drug not only revealed the anti-inflammatory and immunosuppressive properties but also based on the results of various investigations, ß-D-Mannuronic Acid showed the antidiabetic, cardioprotective and anti-tumoral effects. CONCLUSION: ß-D-Mannuronic Acid (M2000) as a novel immunosuppressive drug with NSAID properties along with antidiabetic, cardioprotective and anti-tumoral efficacy showed great tolerability and safety profile. In addition, it has no or mild adverse events compared with many other medicines, therefore this medicament could be considered as a landmark in pharmacology and represent turn point in the treatment of different diseases based on the experimental and in vitro studies explained and clinical and related studies proved.

The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients.

BACKGROUND: Rheumatoid Arthritis (RA) is a complex disease involving an unknown number of genes, and affecting a large number of organs, tissues, and sites across the body. It is affecting approximately 1% of the population worldwide. The safety and therapeutic efficacy of ß-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been demonstrated under in vitro, in vivo examinations and clinical trials phase 1/11 in Ankylosing Spondylitis (AS) patients in addition to phase I/11 and 111 in Rheumatoid Arthritis (RA) patients. OBJECTIVE: In this study, our goal is to evaluate the therapeutic efficacy of oral administration of M2000 on gene expression of the matrix metalloproteinase (MMP2, MMP9) and tissue inhibitor of metalloproteinase (TIMP1, TIMP2) as inflammatory molecules in the progression of rheumatoid arthritis. METHODS: The study has included 15 RA patients who had an insufficient response to the conventional drug. Therefore, mannuronic acid was used as an additive to the conventional regime. The research was a single-blinded study. The dose of M2000 was 500mg orally twice per day for 12 weeks. There were 15 healthy participants considered as control. Blood samples have been collected from both groups once from the healthy control and twice from RA patients before and after treatment with M2000. The Peripheral Blood Mononuclear Cells (PBMCs) were isolated for assessment of the gene expression level of MMP2, MMP9, TIMP1, and TIMP2 using the real-time PCR method. RESULTS: The gene expression level of MMP2 and MMP9 reported a significant reduction in RA patients after treatment with M2000 compared to before treatment. On the other hand, the gene expression level of TIMP2 demonstrated a significant increase in RA patients after treatment with mannuronic acid compared to before treatment, but there was no significant difference between the group of RA patients before treatment and the control group. Vice versa to other molecules, there was no significant difference in the level of TIMP1 in compression with RA patients before and after treatment. CONCLUSION: our findings proved that the ß -D- mannuronic acid) as a novel NSAID with immunosuppressive property has a significant effect on the gene expression level of MMP2, MMP9 and TIMP2 molecules in RA patients.