Diarylheptanoids and Flavonoids from Viscum album Inhibit LPS-Stimulated Production of Pro-inflammatory Cytokines in Bone Marrow-Derived Dendritic Cells

Three new diarylheptanoids, (3S,5R)-3-hydroxy-5-methoxy-1,7-bis(4-hydroxyphenyl)-6E-heptene (1), (3S,5S)-3-hydroxy-5-methoxy-1,7-bis(4-hydroxypheny1)-6E-heptene (2), and (3S)-3-hydroxy-1,7-bis(4-hydroxypheny1)-6E-hepten-5-one (3), four new flavonoid glycosides, 3,7,3'-tri-O-methylquercetin-4'-O-beta-D-apiofuranosyl-(1 -> 2)-O-beta-D-glucopyranoside (4), 7,3'-di-O-methylquercetin-4'-O-beta-D-glucopyranosy1-3-O-[6'''-(3-hydroxy-3-methylglutaroyl)]-alpha-D-glucopyranoside (5), 7,3'-di-O-methylquercetin-4'-O-beta-D-glucopyranosyl-3-O-[(6''''-45'''')-O-1''''-(sinap-4-yl)-beta-D-glucopyranosyl-6'''-(3-hydroxy-3-methylglutaroyl)]-alpha-D-glucopyranoside (6), and (2S)-5-hydroxy-7,3'-dimethoxyflavanone-4'-O-beta-D-apiofuranosyl-(1 -> 5)-O-beta-D-apiofuranosyl-(1 -> 2)-O-beta-D-glucopyranoside (9), and 17 known compounds were isolated from the leaves and twigs of Viscum album. Compounds 1, 4, and 19 significantly inhibited LPS-stimulated production of TNF-alpha, IL 6, and IL-12p40 with IC50 values ranging from 0.09 +/- 0.01 to 8.96 +/- 0.45 mu M. (+)-Medioresinol (13) showed inhibitory effects on LPS-stimulated production of IL-12p40 with an IC50 value of 2.00 +/- 0.15 mu M.