Gallotannin isolated from Euphorbia species, 1,2,6-tri-O-galloyl-beta-D-allose, decreases nitric oxide production through inhibition of nuclear factor-kappa>B and downstream inducible nitric oxide synthase expression in macrophages.

Gallotannins are plant secondary metabolites and are widely included to polyphenolic compounds. Gallotannins are water-soluble polyphenols with wide-ranging biological activities. Nitric oxide (NO) is well known as a mediator of inflammation. Macrophages express inducible nitric oxide synthase (iNOS) and produce NO after lipopoly saccharide (LPS) stimulation. In the present study, we examined the inhibitory effects of seven gallotannins isolated from Euphorbia species (Euphorbiaceae) on the LPS-induced NO production and underlying mechanisms of action. Among the seven gallotannins, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (gallotannin 15) and 1,2,6-tri-O-galloyl-beta-D-allose (gallotannin 23) significantly reduced LPS-induced NO production in macrophages. Gallotannin 15 and 23 (0.1-10 microg/ml) dose-dependently decreased gene expression and production of iNOS. In addition, gallotannin 15 and 23 (0.1-10 microg/ml) dose-dependently inhibited LPS-induced activation of nuclear factor (NF)-kappaB as indicated by inhibition of degradation of I-kappaBalpha, nuclear translocation of NF-kappaB, and NF-kappaB-dependent gene reporter assay. Our results suggest that gallotannins possess an inhibitory effect on the LPS-induced inflammatory reaction.