New benzylresorcinol and benzylstilbene derivatives from the fruits of orchid Galeola nudifolia Lour. with anti-neuroinflammatory activity

Abstract

Galeola nudifolia is a medicinal orchid recognized as a valuable source of structurally diverse natural products with potential therapeutic applications. Its chemical composition and biological activities remain largely unexplored, particularly with respect to anti-neuroinflammatory activity. Bioassay-guided investigation of the non-polar fractions of G. nudifolia fruits led to the isolation of six new compounds, including three benzylresorcinol (1–3) and three benzylstilbene (4–6) derivatives, together with thirteen known compounds (7–19). Their structures were elucidated through comprehensive spectroscopic analyses, including HR-ESIMS, 1D and 2D NMR experiments. The anti-neuroinflammatory activities of all isolated compounds were evaluated in LPS-stimulated BV-2 microglial cells by measuring nitric oxide (NO) production. Compounds 1–6 and 8–13 exhibited significant inhibitory effects on NO production, with IC50 values ranging from 6.59 to 15.79 µM. Notably, compounds 6 (IC50 = 7.77 µM), 10 (IC50 = 7.48 µM), 11 (IC50 = 8.62 µM), and 12 (IC50 = 6.59 µM) showed superior inhibitory potencies compared to the positive control (grossamide, IC50 = 9.23 µM). Immunofluorescence analyses showed that compound 12 reduced iNOS expression and NF-κB p65 nuclear translocation, whereas molecular docking provided qualitative predictions of possible interactions of compounds 6 and 10–12 with iNOS and the IκBα/NF-κB complex. These findings expand the known chemical diversity of G. nudifolia and identify its benzylstilbene derivatives as natural products with anti-neuroinflammatory activity.