Integrated Network Pharmacology Analysis and Experimental Validation to Investigate the Mechanism of Flavan-3-ols and Aromatic resin in Depression

Abstract

Abstract Pharmacological mechanism of the major bioactive flavan-3-ols and aromatic resin intended for management of depression was investigated using network pharmacology, molecular docking, and in vivo studies. Using network pharmacology, the targets for antidepressant activity of two flavan-3-ol components and four aromatic resin components was obtained. Protein-protein interaction and KEGG analysis were used to enrich and investigate key pathways. Molecular docking was carried out to evaluate the targets. Force swim test and Tail suspension test were used to study antidepressant effect. Compound-Target network analysis revealed that many targets were hit by components. The number of nodes are 332 and number of edges are 491. PPI state that our network has significant interaction with (targets) that are involved in depression. The KEGG analysis showed major pathways of flavan-3-ols and aromatic resin in managing depression include controlling the calcium signaling pathway, dopaminergic synapse, glutamatergic pathway, long-term depression, and neurodegenerative pathways. Molecular docking study of EGCG showed the most active compound showing highest affinity with − 7.3 kcal/mol towards serotonin 1A (5-HT1A), -7.4 kcal/mol towards D2, -8.9 kcal/mol for MOA-A. Flavan-3-ols and aromatic resins investigation found to have an antidepressant effect. Flavan-3-ols, and aromatic resin combination significantly (p < 0.05) increase the mobility time in force swim test and tail suspension test and significantly (p < 0.05) decrease the immobility time and time freezing. The network analysis and animal study demonstrated that Flavan-3-ols and aromatic resin had antidepressant characteristics, indicating the necessity for more research to produce a novel antidepressant medication.