Antiinflammatory and neurological activity of pyrithione and related sulfur-containing pyridine N-oxides from Persian shallot (Allium stipitatum).
BACKGROUND
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 (IC₅₀ 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.
Department of Applied Chemistry, University of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic.
Petra
P
Krejčová
Department of Applied Chemistry, University of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic.
Petra
P
Kučerová
Natural History Museum of Denmark, University of Copenhagen, Sølvgade 83, Opg. S., DK-1307 Copenhagen K, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, DK-2100 Copenhagen Ø, Denmark.
Gary I
GI
Stafford
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, DK-2100 Copenhagen Ø, Denmark.
Anna K
AK
Jäger
Department of Applied Chemistry, University of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic. Electronic address: kubecr@centrum.cz.
Roman
R
Kubec
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006735:Horseradish Peroxidase; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D027781:Shallots; D013871:Thiones / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D016861:Cyclooxygenase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D016601:RNA-Binding Proteins; D011963:Receptors, GABA-A; C482440:Sert1 protein, rat; D013871:Thiones; C008704:pyrithione; C013229:pyridine N-oxide; D006735:Horseradish Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; D000110:Acetylcholinesterase
Allium hirtifolium; Allium stipitatum; Cyclooxygenase; Persian shallot; Pyridine N-oxides; Pyrithione