# Antitrypanosomal Activity and Molecular Docking Studies of Lobetyolin From Lobelia rhynchopetalum Hemsl. Root Extract Against Trypanosoma congolense Field Isolates

## TL;DR

This study investigates the antitrypanosomal effects of a plant extract and its compound lobetyolin against a parasite causing animal trypanosomiasis.

## Contribution

The study provides the first evidence of lobetyolin's antitrypanosomal activity and its potential mechanism of action.

## Key findings

- Lobetyolin and the root extract inhibited parasite motility in vitro, with lobetyolin showing faster action.
- Molecular docking revealed strong binding of lobetyolin to trypanothione reductase, suggesting disruption of the parasite's redox balance.
- In vivo testing showed lobetyolin at 100 mg/kg was more effective than the crude extract at 400 mg/kg.

## Abstract

Currently available drugs for trypanosomiasis are few, and their use is limited by toxicity and growing resistance. This highlights the need for safer and more effective alternatives. In this study, the in vitro and in vivo antitrypanosomal activities of an 80% methanol root extract of Lobelia rhynchopetalum and its major constituent were evaluated against Trypanosoma congolense field isolates. Phytochemical separation of the extract yielded lobetyolin (a polyacetylene compound), confirmed through spectroscopic analysis. At 4 mg/mL, both the crude extract and lobetyolin inhibited parasite motility, with lobetyolin acting slightly faster (25 min) than the extract (30 min). The blood incubation assay demonstrated dose‐dependent protection, with 4 mg/mL of DA, the lobetyolin‐rich extract, or pure lobetyolin preventing infection, while lower doses only delayed parasitemia. In vivo testing showed that lobetyolin at 100 mg/kg exhibited stronger activity than the crude extract at 400 mg/kg. Molecular docking demonstrated that lobetyolin binds strongly to the homology‐modeled trypanothione reductase (TR) enzyme of T. congolense, achieving a Glide score of −8.002 kcal/mol, which is close to that of the native ligand (−8.307 kcal/mol). This suggests that lobetyolin may inhibit TR, thereby disrupting the parasite′s redox balance essential for survival. Overall, these findings provide the first evidence supporting the antitrypanosomal activity of L. rhynchopetalum root extract and lobetyolin, providing scientific support to the plant′s traditional use. Further studies are needed to fully validate its therapeutic potential.