GABAergic Modulation and Neurobehavioral Effects of Arjunolic Acid, a Pentacyclic Triterpene Isolated From Combretum Mellifluum Eichler: In Vivo and Molecular Docking Evaluation.

This study investigated the neuropharmacological effects of arjunolic acid, with a particular focus on its anxiolytic and anticonvulsant properties. To this end, in vivo tests were performed on adult zebrafish (Danio rerio) and in silico molecular docking analyses were conducted. Acute toxicity (96 h) was evaluated with doses of 4, 20, and 40 mg/kg (i.p.). Motor activity and anxiety levels induced by the different doses were evaluated using open field and light/dark tests, while the anticonvulsant potential was tested by induction with pentylenetetrazol (PTZ). The GABAergic neuromodulation was also investigated using the antagonist flumazenil and the molecular interaction with the GABAA receptor and carbonic anhydrase II (CAII). The results demonstrated that arjunolic acid is not toxic at the tested doses, but it does cause significant motor alterations, like those caused by diazepam. The compound exhibited an anxiolytic effect and increased the latency to the onset of convulsive seizures. These effects were reversed by flumazenil, confirming mediation by the GABAergic system. These results corroborate the in silico study, which demonstrated a possible allosteric effect of arjunolic acid on the diazepam binding region of the GABAA receptor and on the active site of CAII. However, arjunolic acid is pharmacologically relevant to the central nervous system and may serve as a basis for the development of new therapeutic agents.