Verbascum xanthophoeniceum-derived phenylethanoid glycosides are potent inhibitors of inflammatory chemokines in dormant and interferon-gamma-stimulated human keratinocytes.

BACKGROUND

Verbascum xanthophoeniceum is a representative of mullein species with a strong tradition of use in folk medicine as a remedy in inflammatory and infectious contexts. This plant accumulates phenylethanoid and iridoid metabolites with a partially characterized bioactivity.

METHODS

Here, we compared anti-inflammatory effects of Verbascum xanthophoeniceum crude extract, its fractions, isolated iridoid glycosides, including aucubin, ajugol, harpagide, harpagoside, nigroside III and nigroside VI, and phenylethanoid glycosides verbascoside and forsythoside B in primary cultures of normal human keratinocytes (NHK). The gene expression, synthesis, and release of soluble pro-inflammatory chemokines, such as IL-8, MCP-1 and IP-10, in dormant and IFN-γ-activated NHK were investigated, and IC(50) for each extract/individual substance was determined.

RESULTS

We found that the phenylethanoid glycosides verbascoside and forsythoside B were effective, dose-dependent inhibitors of gene expression and de novo synthesis of all the chemokines, whereas the iridoid glycosides and phenylpropanoid aglycone rosmarinic acid displayed a poor and selective inhibition. Accordingly, the fraction of the crude extract containing verbascoside effectively impaired both spontaneous and induced chemokine expression in NHK.

CONCLUSIONS

This is the first report on the identification of active constituents of Verbascum xanthophoeniceum possessing anti-inflammatory properties towards human keratinocytes. Phenylethanoid glycosides exerted exquisite corticosteroid-like inhibition of pro-inflammatory chemokines at transcriptional and translational levels.