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Introduction of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property Based on Cox-1/Cox-2 Activity and Gene Expression Publisher Pubmed



Mirshafiey A1 ; Taeb M1, 2 ; Mortazavijahromi SS1, 3 ; Jafarnezhadansariha F1, 4 ; Rehm BHA5 ; Esposito E6 ; Cuzzocrea S6 ; Matsuo H7
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  3. 3. Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish, Iran
  4. 4. Department of Immunology, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  5. 5. Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand
  6. 6. Department of Chemical, Biological, Pharmacological and Environmental Sciences, University of Messina, Messina, Italy
  7. 7. Department of Clinical Research, Nagasaki Kawatana Medical Center, Japan
  8. 8. Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan

Source: Pharmacological Reports Published:2017


Abstract

Background The NSAIDs which inhibit the cyclooxygenase (COX) enzymes are among medications widely used to treat pain and inflammation. These drugs cause digestive complications resulting in inhibition of the COX-1 enzyme, while the inhibition of the COX-2 enzyme has therapeutic effects. Therefore research focuses on the production of medications that specifically inhibit the COX-2 enzyme. This study aimed to study the effects of β-D-mannuronic (M2000) acid on the gene expression and activity of COX-1/COX-2 enzymes in order to introduce a novel NSAID for treating inflammatory diseases. Methods The mRNA expression levels of COXs were analyzed with qRT-PCR. Prostaglandin E2 (PGE2) concentration in culture media was determined using ELISA method. Results Our results indicated that the M2000 at low and high dose could significantly reduce the gene expression level of COX-2 compared to the LPS group (p < 0.0001), but no significant reduction was observed in the gene expression level of COX-1 compared to the LPS group. Moreover, it was noticed that this drug strongly and significantly reduced the activity of COX-1/COX-2 enzymes at the three concentrations of 5, 50 and 500 mMol/ml compared to the LPS and arachidonic acid groups (p < 0.0001). Conclusions This study showed that drug M2000 as a novel NSAID with immunosuppressive property is able strongly to inhibit the activity of COX-1/COX-2 enzymes, with suppressing the gene expression of COX-2 specifically. Therefore, based on gene expression findings this drug might be categorized and introduced as a novel NSAID with selective COX-2 inhibitory effect. © 2017 Institute of Pharmacology, Polish Academy of Sciences
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