Spasmolytic Action of Diplotropin, a Furanoflavan from Diplotropis ferruginea Benth., Involves Calcium Blockade in Guinea-Pig Ileum

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).