Isolation and Characterization of 5-(1-Hydroxyethyl)-Dihydro-2-Furanone from Angiopteris evecta with Potent Anti-Inflammatory and Anti-Leukemic Activities

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with poor prognosis, frequent relapse, and treatment-related toxicity. The discovery of novel anti-leukemic agents with improved selectivity remains an urgent clinical need. In this study, rhizomes of Angiopteris evecta, a medicinal plant used in Thai traditional medicine, were collected from twelve locations in Thailand and extracted using solvents of increasing polarity. Among thirty-six crude fractional extracts, the ethyl acetate crude fractional extract from source No. 003 (AE EtOAc No. 003) exhibited the strongest cytotoxic activity against KG-1a and EoL-1 leukemic cell lines, with low toxicity toward normal peripheral blood mononuclear cells. Bioactivity-guided fractionation yielded the ternary mixture, a furanone-rich mixture dominated by 5-(1-hydroxyethyl)-dihydro-2-furanone. The ternary mixture inhibited leukemic cell proliferation by inducing apoptosis, causing cell cycle arrest, and downregulating WT1 expression in EoL-1 cells. Network pharmacology and molecular docking analyses implicated AKT1, MAPK signaling, apoptosis-related pathways, and WT1 as key molecular targets. In addition, AE EtOAc No. 003 and the ternary mixture suppressed TNF-α and IL-6 production in LPS-stimulated macrophages. Collectively, A. evecta-derived furanone compounds represent promising lead candidates for anti-leukemic drug development.