Influence of Origanum vulgare L. on Adenosine Deaminase Activity

It was proved that adenosine deaminase (ADA) accumulates in synovial fluids (SFs) in rheumatoid arthritis (RA), reducing the anti-inflammatory adenosine concentration and exacerbating inflammation. Therefore, ADA inhibiting as an inflammation supporting agent may be beneficial in RA treatment. The quest for the new enzyme inhibitors is a relevant task. The aim of this work was to investigate the influence of the water and ethanol extracts of Origanum vulgare L. (OVL) from Armenian landscape on ADA activity. The influence of the extracts on ex vivo ADA activity in two groups of SFs from RA patients with differing the enzyme activity demonstrated more effective inhibition in SFs with higher ADA activity for both extracts. Two isoforms of ADA were purified to elucidate which one is the main factor responsible for the observed enzyme inhibition. There was no significant difference in inhibition of large isoform of ADA from human erythrocytes and RA SFs. The evaluated IC50 values for small isoform of ADA (SADA) evidenced 1.5 times more effective inhibition in vitro citrullinated enzyme compared to the non-citrullinated one. Considering the accumulation of citrullinated SADA in RA SFs enhances inflammation by metabolizing adenosine, the obtained results suggest OVL is a promising source of anti-inflammatory agent for the development of new therapeutic medicines for RA.