Alkaloids of Hernandia voyronii: Chloroquine-potentiating activity and structure elucidation of herveline D

Further investigation of Hernandia voyronii led to the isolation of a new pavine-benzyltetrahydroisoquinoline (pavine-BTIQ) dimer, herveline D, together with herveline A, five aporphine alkaloids, two morphinane alkaloids, and their biosynthetic precursor, i.e., the BTIQ (S)-reticuline. Hervelines A-D have a moderate intrinsic in vitro antimalarial activity (IC50 in the range of 1.68-3.28 mu M), but displayed different effects ranging from synergism for herveline B and herveline C to simple additive effect for herveline A, and antagonism for herveline D in a chloroquine (CQ) combination evaluation and this was confirmed in vivo for hervelines A and B. Furthermore, the antiplasmoidal activity of CQ was potentiated in vitro by reticuline and its dimethyl derivative laudanosine (for the latter also in vivo), whereas herveline C moderately potentiated in vitro the antiplasmodial activity of herveline D

Broncodilatatory activity of Phytomatodes scolopendria (Burn.) Ching and its bioactive constituents

Phymatodes scolopendria (Burm.) Ching (Polypodiaceae) is widely used in the Eastern coast of Madagascar to treat respiratory disorders. Bioassay-guided fractionation using guinea pig trachea pre-contracted with histamine to monitor the activity led to the isolation of 1,2-benzopyrone (coumarin) as the main active constituent. Effectively, it induced a concentration-dependent relaxation of the histamine with a median effective concentration (EC50) of 35.03g/ml, or carbachol (EC50 = 33.41g/ml) pre-contracted guinea pig trachea, and also provoked 100% relaxation at 72.10g/ml. It was less active either on KCl pre-contracted trachea (EC50 = 130.78g/ml) or endothelium denuded trachea (153.4±22g/ml). It inhibited, in a non-competitive manner, the histamine and the external calcium spasm effect on the isolated trachea but it did not significantly modify the broncho-constrictive activity of KCl. When combined with theophylline, coumarin produced a significant additive relaxing effect on pre-contracted trachea. Furthermore, its bronchodilator effect was not blocked by propranolol. In vivo, pre-treated guinea pig with coumarin showed significant resistance to histamine inhalation, with an adequate dose protecting 50% of the tested animals (AD50) of 75 mg/kg. These results indicate that the bronchodilator effect of coumarin is partly due to the endothelium-dependent tracheal relaxation, and may be mediated through a non-specific tracheal relaxation