M2000: a revolution in pharmacology.
BACKGROUND
The tolerability and the anti-inflammatory and immunosuppressive properties of a novel designed non-steroidal anti-inflammatory drug, M2000 (beta-D-mannuronic acid), were investigated in various experimental models.


METHODS
The anti-inflammatory and immunosuppressive properties of M2000 were tested in experimental models of rheumatoid arthritis (AIA) and multiple sclerosis (EAE). Its therapeutic potency on kidney diseases was studied using experimental models of nephrosis and immune complex glomerulonephritis (ICG). Biocompatibility and pharmacotoxicology assessment of M2000 was carried out using a fibrosarcoma cell line, zymography, and serum and urine determinants.


RESULTS
Data showed that oral and/or i.p. administration of M2000 significantly reduces paw edema and histopathological parameters in arthritic rats. The immunosuppressive property of M2000 could significantly diminish clinical signs and histological erosions in the EAE model. Lymph node cell proliferation assay in EAE confirmed the immunosuppressive efficacy of the tested drug. Our findings in ICG and experimental nephrosis showed that M2000 enables a significant decrease in proteinuria, BUN, serum creatinine and cholesterol, as well as glomerular lesion in M2000-treated rats. Moreover, this drug inhibited MMP-2 activity. The pharmacotoxicology study showed that M2000 is the safest anti-inflammatory and immunosuppressive drug in comparison with dexamethasone and conventional NSAIDs tested. Additionally, M2000 had no ulcerogenic effect on the rat stomach.


CONCLUSIONS
M2000 is the first novel designed NSAID with the lowest molecular weight, no gastro-nephrotoxicity, and therapeutic effects in glomerulonephritis and nephrosis and could be strongly recommended on an extensive scale as the safest drug for decreasing anti-inflammatory reactions.
Mirshafiey
Abbas
A
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. a_mirshafiey@yahoo.com
Cuzzocrea
Salvatore
S
Rehm
Bernd H A
BH
Matsuo
Hidenori
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000906:Antibodies / Q000276:immunology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006838:Hydrocarbons / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012710:Serum Albumin, Bovine / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D006838:Hydrocarbons; D015850:Interleukin-6; D008055:Lipids; D012710:Serum Albumin, Bovine; D020778:Matrix Metalloproteinase 2