Anxiolytic-like Effects by trans-Ferulic Acid Possibly Occur through GABAergic Interaction Pathways

Area of Science:

• Neuroscience
• Pharmacology
• Computational Chemistry

Background:

• Ferulic acid is known for its anxiolytic properties, but its mechanisms remain unclear.
• Trans-ferulic acid (TFA), a stereoisomer, warrants investigation for its potential therapeutic effects.
• Understanding the mechanism of action is crucial for developing new anxiolytic agents.

Purpose of the Study:

• To investigate the anxiolytic effect of trans-ferulic acid (TFA).
• To elucidate the underlying mechanism of TFA's anxiolytic activity using in vivo and computational methods.
• To evaluate TFA's binding affinity to GABA-A receptor subunits.

Main Methods:

• Oral administration of TFA (25, 50, 75 mg/kg) to Swiss albino mice.
• Behavioral tests including open field, hole board, swing box, and light-dark tests.
• Molecular docking simulations to assess binding affinities to GABA-A receptor subunits (α2 and α3).

Main Results:

• TFA exhibited dose-dependent reduction in locomotor activity, indicating a calming effect.
• TFA showed significant binding affinity (-5.8 kcal/mol) to the α2 subunit of the GABA-A receptor.
• Molecular interactions, including hydrogen and hydrophobic bonds, were observed between TFA and the receptor.

Conclusions:

• Trans-ferulic acid (TFA) possesses moderate anxiolytic activity, comparable to Diazepam.
• The anxiolytic effect of TFA is likely mediated through the GABAergic pathway.
• TFA shows promise as a potential anxiolytic agent, warranting further clinical investigation.