Antihypertenseur, Activité Vasorelaxant De Rouppelinia Boivinni (Apocynaceae) Et Etude De Relation Structure-Activité Des Alcaloïdes Indoliques Isolées

Abstract

In the southern and south-western regions of Madagascar, traditional medicine plays an important role in society. Ethnobotanical surveys carried out in these regions have revealed that the plant known under the vernacular name "Feka (nom Mahafaly, Masikoro); Fekambato (Nom Antandroy); Fekakely (Nom Sakalava)" is used by the local population to treat hypertension. The results of biological tests (in-vivo and in-vitro) carried out on the alkaloid extract show improved vasorelaxant activity. These results justify their therapeutic virtues. Bioguided fractionation of the alkaloid extract from the aerial part of this plant resulted in the isolation of two pure products, PX-1 and PX-2. The chemical structures of these two pure products were isolated using spectral analysis methods. The ultraviolet spectrum of the PX-1 molecule recorded by LHPC-UV-DAD shows an absorption maximum at 240nm and 317nm, indicating the presence of an acylindole chromophore in PX-1. The peak at Tr= 2.9min corresponds to the molecular ion peak at m/z =355.20141 [M+H]+, corresponding to the empirical formula C21H26N2O3. Product PX-2 has a molecular weight of m/z = 352.17896 [M+H]+, corresponding to the molecular formula C21H24N2O3, and its UV spectrum recorded by HPLC-UV-DAD shows absorption maxima at 240nm and 317nm consistent with the 2-acyl indole chromophore. Analysis by nuclear magnetic resonance spectroscopy (1D and 2D NMR) confirms that the basic structures of PX-1 and PX-2 are attributed to indole alkaloids. Analysis of the pharmacological mechanism of this plant's vasorelaxant activity shows that the relaxant activity may result from blockade of calcium influx through vascular smooth muscle cells, as the contraction produced by CaCl2 on the aorta in a calcium-free depolarizing medium was inhibited by the alkaloid extract in a concentration-dependent manner with EC50= 0.061±0.0056mg/ml at n=7. Preliminary acute and chronic toxicity studies carried out on the alkaloid extract of this plant showed no significant toxic signs. In perspective, the study of the plant used in medicine to treat TAH enables the isolation of two indole-type alkaloids and the discovery of their mechanisms of pharmacological activity. It's time for researchers to turn to traditional medicine as an inexhaustible source of scientific discovery.