Repository of Research and Investigative Information

Repository of Research and Investigative Information

Rafsanjan University of Medical Sciences

Introduction of beta-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property based on COX-1/COX-2 activity and gene expression

(2017) Introduction of beta-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property based on COX-1/COX-2 activity and gene expression. Pharmacological Reports. pp. 1067-1072. ISSN 1734-1140

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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 b-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 E-2 (PGE(2)) 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. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.

Item Type: Article
Keywords: beta-D-mannuronic COX-1 COX-2 M2000 NSAIDs PGE(2) nonsteroidal antiinflammatory drug prostaglandin synthase messenger-rna cox-2 agent Pharmacology & Pharmacy
Page Range: pp. 1067-1072
Journal or Publication Title: Pharmacological Reports
Journal Index: ISI
Volume: 69
Number: 5
Identification Number: https://doi.org/10.1016/j.pharep.2017.04.015
ISSN: 1734-1140
Depositing User: مهندس مهدی شریفی
URI: http://eprints.rums.ac.ir/id/eprint/4338

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