Tremulane sesquiterpenoids from the endophytic fungus Irpex lacteus with anti-inflammatory activity

Nine tremulane sesquiterpenoids, including two undescribed compounds ( 1 and 2 ) were isolated from Irpex lacteus , an endophytic fungus of Dendrobium officinale , and their structures were unambiguously identified by spectroscopic analyses and ECD calculations. All isolates were evaluated for anti‑inflammatory activity using LPS‑stimulated RAW264.7 macrophages. Compounds 1 and 4 exhibited potent inhibition against nitric oxide production with IC 50 values of 9.88 ± 0.35 μM and 14.32 ± 0.80 μM, respectively, comparable to the positive control dexamethasone (6.55 ± 0.42 μM). Both compounds also markedly decreased the secretion of pro‑inflammatory TNF‑ α , IL‑6 and IL‑1 β in a dose‑dependent manner. Molecular docking results indicated that the compound 1 stably bound to the active sites of iNOS and COX‑2 with binding energies of −6.8 kcal/mol and −6.2 kcal/mol through hydrogen‑bond interactions. This study demonstrates the anti‑inflammatory potential of tremulane sesquiterpenoids from I. lacteus , supporting the further development of fungal metabolites as natural anti‑inflammatory candidates.