Indole Alkaloids of Rauvolfia ligustrina and their Anxiolytic Effects in Adult Zebrafish.

Rauvolfia species are well-known as producers of bioactive monoterpene indole alkaloids (MIAs) which exhibit a broad spectrum of biological activities. A new vobasine-sarpagan-type bisindole alkaloid (1) along with six known monomeric indoles (2, 3/4, 5, and 6/7) were isolated from the ethanol extract from the roots of Rauvolfia ligustrina. The structure of the new compound was elucidated by interpretation of their spectroscopic data (1D and 2D NMR and HRESIMS) and comparison with published data for analog compounds. The cytotoxicity of the isolated compounds was screened in zebrafish (Danio rerio) model. The possible GABAergic (diazepam: positive control) and serotoninergic (fluoxetine: positive control) mechanisms of action in adult zebrafish were also evaluated. No compounds were cytotoxic. Compound 2 and the epimers 3/4 and 6/7 showed mechanism action by GABAA, while compound 1 by serotonin receptor (anxiolytic activity). Molecular docking studies showed that compounds 2 and 5 have a greater affinity by GABAA receptor when compared with diazepam, whereas 1 showed the best affinity for 5HT2AR channel when compared to risperidone.