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

Ethnopharmacological Relevance: 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.

Materials And 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.

Conclusion: 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.