In silico evaluation of Centella asiatica compounds as potential antidepressant agents

Abstract

Major depressive disorder remains a major public health challenge, and plant-derived compounds may provide promising lead structures for antidepressant drug discovery. This study evaluated the predicted interactions of asiatic acid, madecassic acid, and madasiatic acid from Centella asiatica (C. asiatica) with serotonin 1A, dopamine D2, dopamine D3, and mu-opioid receptors (MORs). Molecular docking protocols were validated by redocking co-crystallized ligands, while drug-likeness, oral bioavailability, pharmacokinetic properties, and toxicity were assessed using established in silico tools. Madasiatic acid showed the most favorable predicted binding to serotonin 1A and dopamine D2 receptors, whereas asiatic acid showed the strongest predicted binding to dopamine D3 receptors and moderate binding to MORs. The three C. asiatica-derived compounds generally met common drug-likeness criteria and showed moderate predicted intestinal absorption, possible blood-brain barrier penetration, and no predicted human ether-à-go-go-related gene II inhibition or hepatotoxicity. These findings support further molecular dynamics, receptor-binding, functional, pharmacokinetic, and in vivo validation.