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

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 E (PGE) 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.