Integrative Discovery Through Network Pharmacology and Molecular Docking Approaches of Phenolic Compounds Isolated...

Torreya nucifera, a consumable botanical species native to the southern regions of Korea, has a history of ethnopharmacological application to treat inflammatory conditions. This study employed feature-based molecular networking and integrated with the GNPS database to separate and identify ten phenolic compounds from T. nucifera. We further investigated the therapeutic potential of these isolated compounds and their structural features in the context of rheumatoid arthritis. Protein-protein interaction networks, constructed using compound-target and disease-associated target data, identified NFKB1, RELA, and TNFRSF1A as key hub genes. Gene Ontology (GO) enrichment analysis revealed inflammatory response as the most significantly modulated biological process. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the NF-kB signaling pathway is the most critical of the regulatory cascades influencing the pathogenesis of rheumatoid arthritis. Molecular docking studies verified strong binding affinities between the identified compounds and key target proteins. Furthermore, Western blot results validate that T. nucifera extract suppressed the LPS-activated NF-kB signaling pathways by inhibiting p65 and IκBα phosphorylation. The results underscore the significance of T. nucifera and its anti-inflammatory properties in relation to rheumatoid arthritis, establishing a scientific basis to formulate plant-based products within functional foods, nutraceuticals, and therapeutic interventions targeting rheumatoid arthritis.