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DOI: 10.1055/s-0034-1394540
HERG channel inhibiting activity of Rauvolfia nukuhivensis alkaloid content
Rauvolfia genus is biogeographically widespread in tropical areas including Pacific region. R. nukuhivensis is an endemic species grown in Nuku Hiva island in Marquesas archipelago in French Polynesia, locally called “tu'eiao”, where it is used in traditional medicine for gynecologic care. The structures of the major constituents in R. nukuhivensis bark extract were investigated by using spectroscopic means (UV, HEIRMS, NMR). The occurrence of two β-carboline alkaloids named respectively nukuhivensium and N 12-methylnukuhivensium having indoloquinolizine feature had been previously reported [1]. Continuous work on discovery of new or bioactive compounds from this plant, led to report herein the identification of twelve indole alkaloids belonging to different skeletons (ajmalane, sarpagane, macroline and β-carboline) amongst six of them as new natural compounds. The cytoxicity of the isolated compounds as well as their inhibiting effects on HERG channel activity were evaluated. Cytoxicity assays using neuroblastoma cell line SH-SY5Y showed that four compounds elicited low cellular toxicity after 24 hours incubation. Six components induced reduction of I Kr amplitude (HERG current) performed by whole-cell automated patch clamp electrophysiological recordings on CHO (Chinese Hamster Ovary) recombinant cell line, so showing their inhibiting effect.
Keywords: Rauvolfia nukuhivensis, alkaloids, HERG channels, beta-carboline, macroline
References:
[1] Martin N.J., Prado S., Lecellier G., Thomas O. and Raharivelomanana P. “Nukuhivensiums, indolo [2,3-a] quinoliziniums from the Marquesan plant Rauvolfia nukuhivensis”, Molecules, 2012,17: 12015 – 12022.