Network Pharmacology and Molecular Docking-Based Investigation of Ricinus communis Aerial-Part Constituents against Dental Pain

Abstract Dental pain associated with pulpitis and odontogenic inflammation remains a common clinical problem, while currently used analgesics can cause adverse effects that limit their use. Ricinus communis L. has traditionally been used for painful and inflammatory conditions, but its potential molecular basis in dental pain remains poorly understood. Here, we used an integrated computational pharmacology workflow to investigate the potential mechanisms of R. communis phytoconstituents. 47 phytochemicals were screened for ADME, drug-likeness, and toxicity profiles, resulting in three prioritized compounds; i.e. 3,4-dimethoxy-6,8-dihydroxycoumarin, ferulic acid and p-coumaric acid. Target prediction and intersection with 1,909 dental pain associated genes identified 55 common targets. Protein-protein interaction and centrality analyses highlighted PTGS2, NFKB1, MMP9, STAT3 and EGFR as key network targets. Enrichment and pathway analyses indicated involvement of IL-17, PI3K-AKT, and HIF-1 signaling. Molecular docking showed favorable predicted interactions of the prioritized compounds with the selected targets, while 25 ns molecular dynamics simulations indicated overall stability of the corresponding complexes. Together, these findings suggest that R. communis phytoconstituents may influence interconnected inflammatory and nociceptive pathways and identify candidate compounds and targets for experimental investigation in dental pain.