Antiinflammatory and neurological activity of pyrithione and related sulfur-containing pyridine N-oxides from Persian shallot (Allium stipitatum)

摘要

Ethnopharmacological relevance Persian shallot (Allium stipitatum) is a bulbous plant native to Turkey, Iran and Central Asia. It is frequently used in folk medicine for the treatment of a variety of disorders, including inflammation and stress. Antiinflammatory and neurological activities of pyrithione and four related sulfur-containing pyridine N-oxides which are prominent constituents of Allium stipitatum were tested. Methods The antiinflammatory activity was tested by the ability of the compounds to inhibit cyclooxygenase (COX-1 and COX-2), whereas the neurological activities were evaluated by assessing the compounds ability to inhibit monoamine oxidase-A (MAO-A) and acetylcholinesterase (AChE). The compounds' affinity for the serotonin transport protein (SERT) and the GABAA-benzodiazepine receptor were also investigated. Results 2-[(Methylthio)methyldithio]pyridine N-oxide showed very high antiinflammatory effects which are comparable with those of common pharmaceuticals (IC50 of 7.8 and 15.4 μM for COX-1 and COX-2, respectively). On the other hand, neurological activities of the compounds were rather modest. Some compounds moderately inhibited AChE (IC 50 of 104-1041 μM) and MAO-A (IC50 of 98-241 μM) and exhibited an affinity for the SERT and GABAA-benzodiazepine receptor. Conclusions Our findings may help to rationalize the wide use of Persian shallot for the treatment of inflammatory disorders.