Anxiolytic Effects of Indole Alkaloids From <i>Rauvolfia ligustrina</i> in Adult Zebrafish: Involvement of the GABAergic and 5‐HT Systems
Benzodiazepines are widely used in the treatment of anxiety, but their use may be interrupted due to side effects. This study evaluated the indole alkaloids isocarapanaubine (indole alkaloid 1 [AIN1]) and 18-β-hydroxy-3-epi-α-yohimbine (indole alkaloid 2 [AIN2]), extracted from Rauvolfia ligustrina, in adult zebrafish. Three doses (4, 12, and 20 mg/kg) were tested, along with dimethyl sulfoxide (DMSO) 3% and Diazepam (4 mg/kg) in toxicity, locomotion, and anxiolytic effect assays. AIN1 and AIN2 showed low toxicity (lethal dose capable of killing 50% of the animals >20 mg/kg) and reduced locomotor activity. Both exhibited anxiolytic effects, with AIN1 acting through the GABAergic system and AIN2 via the serotonergic pathway (5-HT<sub>3A</sub>). Interactions with receptors were confirmed by molecular docking, and drug metabolism and pharmacokinetics studies indicated that AIN2 is promising in terms of permeability and safety in the central nervous system.
Authors
- Otília Deusdênia Loiola Pessoa (ORCID: https://orcid.org/0000-0002-1617-7586)
- Hélcio Silva dos Santos (ORCID: https://orcid.org/0000-0001-5527-164X)
- Hemerson Iury Ferreira Magalhães (ORCID: https://orcid.org/0000-0001-7139-8712)
- Nádia Aguiar Portela Pinheiro (ORCID: https://orcid.org/0000-0002-5244-5613)
- Sônia Maria Costa Siqueira (ORCID: https://orcid.org/0000-0001-8556-3715)
- Ivana Carneiro Romão (ORCID: https://orcid.org/0000-0002-6151-9397)
- Amanda Maria Barros Alves (ORCID: https://orcid.org/0000-0003-3846-7311)
- Jane Eire Silva Alencar de Menezes (ORCID: https://orcid.org/0000-0001-9632-5464)
- Emmanuel Silva Marinho (ORCID: https://orcid.org/0000-0002-4774-8775)
- Andreia Ferreira de Castro Gomes (ORCID: https://orcid.org/0000-0002-0567-064X)
- Márcia Machado Marinho (ORCID: https://orcid.org/0000-0002-7640-2220)
Institutions
- Universidade Estadual do Ceará (BR)
- Universidade Federal do Ceará (BR)
- State University of Vale do Acaraú (BR)
- University of Minho (PT)
Publication Details
- Journal
- Chemistry & Biodiversity
- Published
- 2025-06-03
- DOI
- https://doi.org/10.1002/cbdv.202500016
- Primary Topic
- Alkaloids: synthesis and pharmacology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico