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Effects of phenylethanoid glycosides from Digitalis purpurea L. on the expression of inducible nitric oxide synthase

We have isolated four different phenylethanoid glycosides (purpureaside A, desrhamnosyl acteo‐side, calceolarioside B and plantainoside D) from the leaves of Digitalis purpurea (foxglove). The effects of these glycosides on activator protein‐1 (AP‐1)‐mediated inducible nitric oxide synthase (iNOS) gene expression in the Raw264.7 macrophage cell line have been studied. Of these four glycosides, purpureaside A potently inhibited iNOS induction by lipopolysaccharide (LPS). Increase in iNOS mRNA by LPS was completely suppressed by purpureaside A. Purpureaside A did not significantly affect LPS‐inducible nuclear factor‐kB (NF‐kB) activation or the nuclear translocation of p65. Moreover, a reporter gene assay using AP‐1 specific luciferase reporter revealed that the enhanced activity of AP‐1 by LPS was completely abolished in cells treated with purpureaside A. These results demonstrated that purpureaside A inhibited LPS‐inducible iNOS expression in macrophages through the suppression of AP‐1, but not of NF‐kB.