Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation to Explore Predicted Molecular Associations Between Fraxini Cortex Constituents and Intestinal Inflammation in Laying Hens

Abstract

Simple Summary Intestinal inflammation can impair gut health, nutrient utilization, and immune balance in laying hens. Fraxini Cortex is a traditional herbal medicine containing multiple reported bioactive compounds, but its possible molecular relationships with intestinal inflammation in poultry remain unclear. In this entirely in silico study, reported Fraxini Cortex constituents were screened and linked with intestinal inflammation-related targets, followed by human-to-Gallus gallus orthologue mapping, chicken-specific protein interaction and pathway analyses, molecular docking, molecular dynamics simulations, and MM/GBSA calculations. Thirty-eight candidate constituents and 133 chicken homologous targets were retained, and 13 core candidate targets were further prioritized. Caffeic acid and scopoletin showed prominent positions in the computational analyses, while the predicted targets were mainly associated with immune recognition, receptor and kinase signaling, epithelial integrity, cell survival, tissue remodeling, and lipid-mediator-related processes. Replicated molecular dynamics simulations and binding-energy calculations further characterized the predicted caffeic acid–MMP9 and scopoletin–ESR1 complexes. These findings identify candidate compounds, targets, and pathways that may be relevant to intestinal inflammation in laying hens and provide testable hypotheses for future chicken-specific experimental studies.