Spasmolytic action of diplotropin, a furanoflavan from Diplotropis ferruginea Benth., involves calcium blockade in guinea-pig ileum

Abstract

Diplotropis ferruginea Benth. (Fabaceae) is a tree popularly known in Northeastern Brazil as "sucupira-preta". In the present work, the isolation, identification and pharmacological activity of a furanoflavan-type flavonoid (2,3-trans-3,4-trans)-3,4,5,8-tetramethoxy-(6,7,2″,3″)- furanoflavan, which received the trivial name diplotropin is reported. The structure was determined by means of spectroscopic techniques, especially EIMS and 1D and 2D NMR. Diplotropin (10-8 - 3·10-4 M) inhibited the phasic contractions induced by both acetylcholine (IC50 = 4.6 ± 0.8·10-5 M) and histamine (IC50 = 2.3 ± 1.1·10-5 M) in guinea-pig ileum. Diplotropin relaxed the ileum pre-contracted with KCl (EC50 = 3.9 ± 1.1·10-6 M), acetylcholine (EC50 = 3.7 ± 1.6·10-6 M) and histamine (EC50 = 4.4 ± 1.4·10-5 M) in a concentration-dependent manner. As the maintenance of tonic contraction induced by these contractile agents involves Ca2+ influx through voltage-dependent Ca2+ channels, it is suggestive that this relaxation may be due to the blockade of Ca2+ influx through those channels. This hypothesis was confirmed by the observation that diplotropin antagonized (pD′2 = 4.83 ± 0.37) CaCl2 induced contractions in Ca2+-free depolarizing medium (IC50 = 1.5 ± 0.8·10-5 M). © 2005 Verlag der Zeitschrift für Naturforschung.