INTEGRATED NETWORK PHARMACOLOGY, TRANSCRIPTOMIC VALIDATION, AND MOLECULAR DOCKING ANALYSIS OF ANTI-INFLAMMATORY MECHANISMS OF COLUMBIN

Abstract

The intricacy of chronic inflammation's interrelated signaling pathways has led to the perception that multi-target treatment tactics are more successful than single-target approaches, emphasising the necessity of system-level research. Columbin, a furanoditerpenoid lactone discovered from the Tinospora species, has been shown to have anti-inflammation properties; however, the underlying molecular mechanisms remain unknown. This study used an integrated computational approach to thoroughly investigate columbin's multi-target anti-inflammatory properties. Four computational techniques were used to suggest potential targets, which were then confirmed against genes linked with inflammation using GeneCards, DisGeNET, and transcriptome profiling (GSE55235). Protein-protein interaction (PPI) analysis indicated eight hub genes (ESR1, JAK1, JAK2, MAPK1, STAT3, HSP90AA1, PIK3R1, and PTPN11) that contribute to significant inflammatory signaling. Molecular docking demonstrated favorable binding affinities. Molecular docking yielded favorable binding affinities (ΔG: -6.9 to -8.6 kcal/mol) and protocol validation using co-crystal ligand redocking (RMSD <2 Å). External validation with an independent rheumatoid arthritis dataset (GSE55457) revealed differential expression of hub genes (2 of 8 significant, FDR<0.05) with diagnostic potential (5 of 8 genes, AUC>0.70). Immune infiltration research indicated strong relationships between hub gene expression and immune cell types, notably neutrophils and macrophages. ADMET profiling revealed favorable oral bioavailability with anticipated hepatotoxicity, requiring experimental confirmation. These findings provide the first comprehensive characterisation of columbin's multi-target anti-inflammatory mechanism, as well as a computational framework that may be used to phytochemical drug development.