Potential improvement of Isaria cicadae Miquel spores oil(ICSO)alleviate TNBS-induced fibrosis of Caco-2 cells by down-regulating the activation of EGFR and SRC in the MEK/ERK and PI3K/Akt pathways

The natural oil extracted from Isaria cicadae Miquel (ICSO), a rare mushroom species, has demonstrated efficacy in alleviating intestinal fibrosis associated with Crohn's disease (CD), although its precise mechanisms remain unclear. This study employed an integrated approach combining network pharmacology, molecular docking, and experimental validation to investigate ICSO's therapeutic potential. ICSO obtained through Soxhlet extraction was characterized by GC–MS, revealing 21 components including 16 fatty acids (84.82 % of total composition). In a TNBS-induced Caco-2 cell fibrosis model, ICSO (20-200 μg/mL) dose-dependently attenuated intestinal fibrosis, significantly reducing hydroxyproline accumulation (P < 0.05) and suppressing type I and II collagen deposition (P < 0.01). Furthermore, Consistent with network pharmacology predictions, ICSO (50, 100, and 200 μg/mL) markedly inhibited EGFR overexpression, suppressed SRC activation, while downregulating AKT (P < 0.001) and MAPK1 phosphorylation (P < 0.05). These coordinated mechanisms effectively ameliorated epithelial-mesenchymal transition (EMT) and prevented intestinal fibrosis progression in CD.