Biflavonoids and bi- and tricoumarins from Daphne mezereum and inhibition of TNF-α secretion

Abstract

Daphne mezereum L. (Thymelaeaceae) was an important medicinal plant in Norway during the 18th and 19th centuries and used against diseases such as diarrhea, swelling, stomach pain, and tuberculosis. Five previously undescribed phenolic compounds, including two biflavonoids with a catechin core structure, two tricoumarins, and one bicoumarin, together with ten known compounds were isolated from a 50% EtOH extract of the bark of D. mezereum. Using NMR, HRESIMS, acid hydrolysis, and circular dichroism spectra, the biflavonoids were identified as 3′-hydroxygenkwanol A and 3′-hydroxydihydrodaphnodorin B, and the coumarins were identified as 3‴-O-acetyltriumbellin, triumbellin 4‴-O-β-d-glucopyranoside, and daphnogitin-7-O-β-d-glucopyranoside. The absolute configuration of dihydrodaphnodorin B was for the first time established as 2R, 3S, 2″S, 3″S. Daphnin, syringin, 3′-hydroxydihydrodaphnodorin B, dihydrodaphnodorin B, and neochamaejasmin A and B were identified as the major secondary metabolites in the extract. Neochamaejasmin A and B showed the most potent inhibition of TNF-α secretion in Con A stimulated peripheral blood mononuclear cells (PBMCs) with 71.3 ± 3.4 and 83.5 ± 11.5% inhibition, respectively, at 50 μM.