GC-MS characterization and in-silico evaluation of TNF-α binding efficacy of leaf extract from Abies spectabilis (D. Don) Spach.

Abstract

Abies spectabilis, a medicinal conifer native to the Himalayas, has long been recognized in traditional medicine for its therapeutic properties, particularly in the treatment of inflammatory and respiratory disorders. This study aimed to investigate the phytochemical constituents of its aqueous leaf extract and evaluate the anti-inflammatory potential of its bioactive compounds through in-silico approaches. Qualitative phytochemical analysis confirmed the presence of flavonoids, alkaloids, coumarins, tannins, and naphthoquinones, known for their antioxidant and immunomodulatory properties. Subsequent GC-MS profiling revealed ten major compounds, including Pyrazole[4,5-b]imidazole, siloxanes, and heterocyclic derivatives. The anti-inflammatory potential of the leaf extract was estimated through COX-1 and COX-2 inhibition assays, which yielded IC₅₀ values of 28.757 ± 0.045 µg mL^-1 and 16.821 ± 0.028 µg mL^-1, respectively. A selectivity index indicated preferential inhibition of COX-2, supporting its targeted anti-inflammatory activity. Molecular docking studies were conducted against the pro-inflammatory cytokine TNF-α (PDB ID: 1A8M), where Pyrazole[4,5-b]imidazole exhibited the strongest binding affinity with a glide score of -7.306 kcal/mol. Molecular dynamics (MD) simulations further confirmed the stability of this ligand-protein complex, with minimal RMSD and RMSF fluctuations, persistent interactions, and favourable conformational dynamics. The compound shows promising in-silico potential and may warrant further investigation in preclinical settings.