# Europium Metal Complex [Eu(dbm)3.LAP] Promotes Antinociceptive Behavior via TRPA1 Neuromodulation and an Anti‐Inflammatory Effect in Adult Zebrafish

## TL;DR

This paper shows that a europium complex reduces pain and inflammation in zebrafish by targeting TRPA1 receptors and has good brain permeability.

## Contribution

The first evaluation of a europium complex's antinociceptive and anti-inflammatory effects via TRPA1 modulation in zebrafish.

## Key findings

- Eu(dbm)3.LAP reduced inflammation and oxidative stress in zebrafish tissues.
- In silico analysis showed high brain permeability and low cardiotoxicity for the complex.
- Molecular docking confirmed stable interactions with TRPA1 receptor residues.

## Abstract

The identification of antinociceptive compounds often relies on animal models such as zebrafish, in which TRPA1 activation induces hyperlocomotion. This study presents the first evaluation of the anti‐inflammatory and antinociceptive properties of the europium complex [Eu(dbm)3.LAP], derived from Lapachol, and investigates its possible interaction with the TRPA1 channel in adult zebrafish. The complex was administered intramuscularly, and its effects were compared with camphor and morphine controls. In vivo findings were integrated with in silico docking, molecular dynamics simulations, and predictive pharmacokinetic analysis. Eu(dbm)3.LAP (40 mg/kg, oral) was effective specifically in the inflammatory phase, and its effect was blocked by camphor, indicating TRPA1 modulation. The compound also reduced carrageenan‐induced inflammation and attenuated oxidative stress in nerve and liver tissues. In silico predictions indicated high intestinal absorption (∼100%), good blood–brain permeability (LogBB = 0.62), and low cardiotoxicity (pKihERG = 7.73). Docking revealed a binding energy of −8.1 kcal·mol−
1 with stable interactions involving LYS1046, TYR1049, and LYS1052. Molecular dynamics confirmed stability over 100 ns and preservation of key hydrogen bonds, supporting the modulatory potential observed in vivo.

The [Eu(dmb)3.LAP] complex was synthesized and characterized as a potent neuromodulatory and anti‐inflammatory agent. Molecular docking and ADMET analyses revealed a candidate that is permeable to the brain barrier and targets TRPA1 receptors. In vivo assays using adult zebrafish confirmed a significant reduction in inflammatory responses, highlighting this complex as a promising therapeutic strategy for neuroinflammatory disorders.