Chemical profiling and antioxidant potential of the ethanolic extract of the Odontotermes formosanus fungus comb: an integrated LC–MS/MS and computational study

Abstract Fungus combs of fungus-growing termites are complex symbiotic matrices formed through termite feeding and digestion of plant substrates, followed by continuous transformation by symbiotic Termitomyces fungi and associated microorganisms. Although extracts from the fungus combs of some fungus-growing termite species have been reported to exhibit antioxidant activity, the chemical composition and biological properties of the fungus comb of Odontotermes formosanus remain poorly characterised. In the present study, untargeted liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to characterise the ethanolic extract of the O. formosanus fungus comb (OFCE), and its antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging and ferric reducing antioxidant power (FRAP) assays. As an exploratory extension, ageing-related database targets were used as a biological context, and target prediction, network analysis, molecular docking, and 100 ns molecular dynamics simulations were integrated to prioritise selected putative annotations and predicted ligand–target relationships. Azelaic acid and N-acetyltryptophan were among the candidates prioritised for further evaluation. Under the computational models and simulation conditions used, the two epidermal growth factor receptor (EGFR)–ligand complexes exhibited conformational compatibility and maintained relatively stable conformational states during portions of the simulations. Collectively, these findings indicate that the O. formosanus – Termitomyces fungus-comb system contains a chemically diverse pool of ethanol-extractable small molecules accompanied by measurable antioxidant activity, thereby providing candidate leads for subsequent structural confirmation, source attribution, quantitative analysis, and activity validation.