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

Herbert Magalhães de Sousa; Alison Batista da Silva; Maria Kueirislene Amâncio Ferreira; Antonio Wlisses da Silva; Jane Eire Silva Alencar de Menezes; Emmanuel Silva Marinho; Márcia Machado Marinho; Helcio Silva dos Santos; Otilia Deusdênia Loiola Pessoa

doi:10.1055/a-2058-3710

Planta Medica, Table of Contents

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

Authors

Herbert Magalhães de Sousa

¹Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza-CE, Brazil
Alison Batista da Silva

¹Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza-CE, Brazil
Maria Kueirislene Amâncio Ferreira

²Programa de Graduação em Ciências Naturais, Universidade Estadual de Ceará, Fortaleza-CE, Brazil
Antonio Wlisses da Silva

³Programa de Graduação em Biotecnologia, Universidade Estadual de Ceará, Fortaleza-CE, Brazil
Jane Eire Silva Alencar de Menezes

²Programa de Graduação em Ciências Naturais, Universidade Estadual de Ceará, Fortaleza-CE, Brazil
Emmanuel Silva Marinho

²Programa de Graduação em Ciências Naturais, Universidade Estadual de Ceará, Fortaleza-CE, Brazil
Márcia Machado Marinho

⁴Curso de Química, Universidade Estadual do Vale do Acaraú, Sobral-CE, Brazil
Helcio Silva dos Santos

⁴Curso de Química, Universidade Estadual do Vale do Acaraú, Sobral-CE, Brazil
Otilia Deusdênia Loiola Pessoa

¹Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza-CE, Brazil

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 GABA_A, 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 GABA_A 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

Full Text

References

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