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Planta Med 2023; 89(10): 979-989
DOI: 10.1055/a-2058-3710
Biological and Pharmacological Activity
Original Papers

Indole Alkaloids of Rauvolfia ligustrina and Their Anxiolytic Effects in Adult Zebrafish

Herbert Magalhães de Sousa 
1   Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza-CE, Brazil
,
Alison Batista da Silva
1   Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza-CE, Brazil
,
Maria Kueirislene Amâncio Ferreira
2   Programa de Graduação em Ciências Naturais, Universidade Estadual de Ceará, Fortaleza-CE, Brazil
,
Antonio Wlisses da Silva
3   Programa de Graduação em Biotecnologia, Universidade Estadual de Ceará, Fortaleza-CE, Brazil
,
Jane Eire Silva Alencar de Menezes
2   Programa de Graduação em Ciências Naturais, Universidade Estadual de Ceará, Fortaleza-CE, Brazil
,
Emmanuel Silva Marinho
2   Programa de Graduação em Ciências Naturais, Universidade Estadual de Ceará, Fortaleza-CE, Brazil
,
Márcia Machado Marinho
4   Curso de Química, Universidade Estadual do Vale do Acaraú, Sobral-CE, Brazil
,
Helcio Silva dos Santos
4   Curso de Química, Universidade Estadual do Vale do Acaraú, Sobral-CE, Brazil
,
Otilia Deusdênia Loiola Pessoa 
1   Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza-CE, Brazil
› InstitutsangabenThis work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (No. 420454/2016-0 and 310183/2020-0).
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Abstract

Rauvolfia species are well known as producers of bioactive monoterpene indole alkaloids, 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 of 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 a zebrafish (Danio rerio) model. The possible GABAergic (diazepam as the positive control) and serotoninergic (fluoxetine as the 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 a mechanism action by GABAA, while compound 1 showed a mechanism action by a serotonin receptor (anxiolytic activity). Molecular docking studies showed that compounds 2 and 5 have a greater affinity by the GABAA receptor when compared with diazepam, whereas 1 showed the best affinity for the 5HT2AR channel when compared to risperidone.

Key words

Rauvolfia ligustrina - Apocynaceae - alkaloids - zebrafish - Danio rerio - anxiolytic effect

Supporting Information

    HRESIMS of compound 1 and NMR spectra of compounds 1–6/7 are available in the Supporting Information.

  • Ergänzendes Material


Publikationsverlauf

Eingereicht: 02. August 2022

Angenommen nach Revision: 20. März 2023

Accepted Manuscript online:
20. März 2023

Artikel online veröffentlicht:
15. Mai 2023

© 2023. Thieme. All rights reserved.

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