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

Abstract

Ethnopharmacological relevancePersian 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. MethodsThe 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. Results2-[(Methylthio)methyldithio]pyridine N-oxide showed very high antiinflammatory effects which are comparable with those of common pharmaceuticals (IC50 of 7.8 and 15.4µM for COX-1 and COX-2, respectively). On the other hand, neurological activities of the compounds were rather modest. Some compounds moderately inhibited AChE (IC50 of 104–1041µM) and MAO-A (IC50 of 98–241µM) and exhibited an affinity for the SERT and GABAA–benzodiazepine receptor. ConclusionsOur findings may help to rationalize the wide use of Persian shallot for the treatment of inflammatory disorders.