# Anxiolytic Effects of Indole Alkaloids From Rauvolfia ligustrina in Adult Zebrafish: Involvement of the GABAergic and 5‐HT Systems

## TL;DR

This study explores two indole alkaloids from Rauvolfia ligustrina for their anxiolytic effects in zebrafish, showing potential as safer alternatives to benzodiazepines.

## Contribution

The novel contribution is identifying AIN1 and AIN2 as anxiolytic compounds with distinct mechanisms involving GABAergic and serotonergic systems.

## Key findings

- AIN1 and AIN2 showed low toxicity and anxiolytic effects in zebrafish.
- AIN1 acts via the GABAergic system, while AIN2 acts via the 5-HT3A receptor pathway.
- AIN2 demonstrated promising permeability and safety in the central nervous system.

## Abstract

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‐HT3A). 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.