Integrated network pharmacology analysis and experimental validation to investigate the mechanism of Flavan-3-ols and aromatic resins in depression.

ABSTRACT

The present investigation delved into the pharmacological mechanisms underlying the management of depression through Flavan-3-ols and Aromatic Resins, employing in silico and in vivo methodologies. Network pharmacology was utilized to identify targets associated with the antidepressant activity of Flavan-3-ols and Aromatic Resins. Protein-protein interaction and KEGG analyses were conducted to enrich and explore key pathways. Molecular docking and simulation studies were executed to assess the targets. The antidepressant effects were studied using the Forced Swim Test and Tail Suspension Test on both unstressed mice and those subjected to the chronic unpredictable mild stress (CUMS) paradigm. The Compound-Target network analysis revealed a substantial impact of the components on numerous targets, with 332 nodes and 491 edges. Protein-protein interaction analysis indicated significant interactions with targets implicated in depression. KEGG analysis highlighted major pathways, including neuroactive ligand-receptor interaction, dopaminergic synapse, and long-term depression. Docking studies on EGCG demonstrated binding energies of -7.2 kcal/mol for serotonin 1 A (5-HT1A), -7.9 kcal/mol for D2, and - 9.6 kcal/mol for MOA-A. Molecular dynamics simulation indicated minute fluctuation, hence suggesting stable complexes formed between small molecules and proteins. The combination of Flavan-3-ols and Aromatic Resins significantly increased mobility time (p < 0.05) in the Forced Swim Test and Tail Suspension Test, while significantly decreasing immobility time and time freezing (p < 0.05) in both unstressed and CUMS mice. This study demonstrated the antidepressant characteristics of Flavan-3-ols and Aromatic Resins, underscoring the need for further research to develop a novel antidepressant medication.