Network Pharmacology Analysis and Experimental Validation to Investigate the Mechanism of Flavan-3-Ols and Aromatic Resin in Anxiety

Abstract

Abstract Purpose Pharmacological mechanism of the major bioactive flavan-3-ols and aromatic resin intended for management of anxiety was investigated using network pharmacology, molecular docking, and in vivo studies. Methods Using network pharmacology, the targets for antianxiety 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. Elevated plus maze, open field test, light and dark, actophotometer and hole board test were used to study antianxiety effect. Results 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 anxiety. The KEGG analysis showed major pathways of flavan-3-ols and aromatic resin in managing anxiety are through controlling the calcium signaling route, cholinergic synapses, dopaminergic synapses, and the estrogen signaling system. Molecular docking study of EGCG showed the most active compound showing highest affinity with binding energy − 7.4 kcal/mol towards D2, -7.8 kcal/mol towards GABA, -9.2 kcal/mol for serotonin. An elevated plus maze investigation found the antianxiety impact of flavan-3-ols and aromatic resin. Flavan-3-ols, and aromatic resin combination significantly (p < 0.05) increase the number of entries in the open arm and the total time spent in the open arm. In the light dark test, there was a highly significant (p < 0.01) increase in the time spent in the light region. The time spent in the center area and the number of entries in the center area highly significant (p < 0.01) increases considerably in the open field test. In the hole board test, the number of head dips was substantially (p < 0.01) higher. The number of photo beam interruptions significantly (p < 0.05) increases in the actophotometer. Conclusion The network analysis and animal study demonstrated that Flavan-3-ols and aromatic resin had antianxiety characteristics, indicating the necessity for more research to produce a novel antianxiety medication.