Assessment of Rauvolfia nukuhivensis: from uses to biological ac-tivities and chemodiversity

Rauvolfia genus, biogeographically widespread in tropical areas, includes many species used in traditional medicine. Studies of these species showed that their uses are related to their bioactive content mostly composed by alkaloid compounds. Rauvolfia nukuhivensis, called locally “tueiao”, is an endemic species grown in Nuku-Hiva island located in Marquesas archi-pelago where the bark is used for intimate woman care [1]. Ethnopharmacological approach was adopted to assess this plant. For that purpose, firstly, we checked if the plant extract played an antiseptic role within antimicrobial effects by testing the extract and contents on bacterial and fungi strains (Escherichia coli, Staphylococcus aureus, Candida albicans and Aspergillus niger) and bioassay results showed moderate to low activities. Then, we supposed that traditional medicinal uses of this plant may be linked to biological activities having close relationship with secretory mechanisms regulation. This hypothesis was investigated by the ion channels inhibition related to osmotic exchanges and then, inhibiting effects on hNav1.6 currents and hERG channel were so investigated. Some alkaloidal constituents, and more especially nukuhivensiums, were shown to significantly induce a reduction of IKr amplitude (hERG current). According to these biological activities, a computational study through docking was performed in order to illustrate these results [2,3]. The chemodiversity of the alkaloids from the bark of this plant was assessed by three inte-grated approaches mainly: structural elucidation, phylogenetic analysis and a putative biosynthesis hypothesis statement. Structural elucidation by spectroscopic means (MS, NMR) led to the identification of 13 major constituents belonging to four distinct indole alkaloid skeletons (ajmalane, sarpagane, macroline and β-carboline) within six new naturally occuring compounds. As the Rauvolfia genus is well distributed in the Pacific region, we carried out a phylogenetic study (using DNA barcoding method) of Rauvolfia species, endemic or indigenous in Oceania, as a second approach, aiming to a better understanding of the occurence and distribution of these alkaloids. The very rare co-occurence of these alkaloids belonging to four different skeletons inspired to set up a putative biosynthesis of these components, as a third way of investigation of their chemodiversity [2 – 4].

Acknowledgements: The “Ministère de l'Enseignement Supérieur et de la Recherche” of the French government is acknowledged for providing PhD grant. We are thankful to J.F. Butaud and to French Polynesia DIREN department for sample collection, plant material identification and helpful discussions. The authors wish to thank J.-M. Guigonis (Plate-Forme Bernard Rossi) for HRESIMS measurements.

Keywords: Rauvolfia nukuhivensis, Apocynaceae, ethnopharmacology, indole alkaloids, hERG channel activity inhibition, Docking calculation.

References:

[1] Girardi C, Butaud JF, Ollier C, Ingert N, Weniger B, Raharivelomanana P, Moretti C. Herbal medicine in the Marquesas islands, J Ethnopharmacol 2015; 161: 200 – 213.

[2] Martin NJ, Prado S, Lecellier G, Thomas O, Raharivelomanana P. Nukuhivensiums, indolo [2,3-α] quinoliziniums from the Marquesan plant Rauvolfia nukuhivensis. Molecules 2012; 17: 12015 – 12022.

[3] Martin NJ, Ferreiro SF, Barbault F, Nicolas M, Lecellier G, Paetz C, Gaysinski M, Alonso E, Thomas OP, Botana LM, Raharivelomanana P. Indole alkaloids from the Marquesan plant Rauvolfia nukuhivensis and their effects on ion channels. Phytochemistry 2015; 109: 84 – 65.

[4] Martin NJ, Nicolas M, Lecellier G, Raharivelomanana P. Isolation and characterization procedure for indole alkaloids from the Marquesan plant Rauvolfia nukuhivensis, Bio-protocol 2015; 5: e1625.