Mechanisms Underlying the Tracheorelaxant Effect of Vitex agnus-castus Extract

Abstract

Medical plants, including Vitex agnus-castus L., Lamiaceae, were used in folk medicine for a long time; however, V. agnus-castus mechanisms of actions on trachea are not known. This study was attempted to give evidence for medicinal use of V. agnus-castus as a relaxant and to identify its underlying mechanisms. To this end, V. agnus-castus extract was extracted with ethanol and tested in rabbit tracheal smooth muscle using isolated organ baths. The V. agnus-castus extract (0.15–60 mg/ml) relaxed against acetylcholine-induced constriction in isolated rabbit tracheal smooth muscle, in vitro. Further, V. agnus-castus extract (0.15–75 mg/ml) shown relaxing effects in carbachol and high K-induced contraction of rabbit tracheal smooth muscle, implying antimuscarinic and calcium channel blocking activities. The addition (preincubation) of L-NAME (inhibitor of nitric oxide synthases), as well as indomethacin (cyclooxygenase inhibitor), inhibited (102%, 95% respectively) relaxing effects induced by V. agnus-castus extract precontracted with carbachol. On the other hand, bradykinin (stimulator of nitric oxide synthases) and zaprinast (phosphodiesterase inhibitor) further potentiated (40%, 41%, respectively) relaxing-induced effects by the V. agnus-castus extract. Our data suggest that V. agnus-castus extract airway-relaxing properties have muscarinic antagonism, are dependent on calcium blockade, and are at least partly mediated by the nitric oxide/cyclic guanosine monophosphate- and cyclooxygenase-1-prostaglandin E2-dependent mechanisms. These effects justify V. agnus-castus extract use in various respiratory disorders.