Phenylpropanoids have several highly significant biological properties in both 
plants and animals. Four phenylpropanoid glycosides (PPGs), verbascoside (VB), 
forsythoside B (FB), echinacoside (EC) and campneoside I (CP), were purified and 
tested for their capability to activate NRF2 and induce phase II cytoprotective 
enzymes in a human keratinocyte cell line (HaCaT). All four substances showed 
similar strong antioxidant and radical-scavenging activities as determined by 
diphenylpicrylhydrazyl assay. Furthermore, in HaCaT cells, FB and EC are strong 
activators of NRF2, the nuclear transcription factor regulating many phase II 
detoxifying and cytoprotective enzymes, such as heme oxygenase 1 (HMOX1). In 
HaCaT cells, FB and EC (200 μM) induced nuclear translocation of NRF2 protein 
after 24 h and reduced nuclear protein levels of BACH1, a repressor of the 
antioxidant response element. FB and EC greatly HMOX1 mRNA levels by more than 
40-fold in 72 h. Cytoplasmic HMOX1 protein levels were also increased at 48 h 
after treatment. VB was less active compared to FB and EC, and CP was slightly 
active only at later times of treatment. We suggest that hydroxytyrosol (HYD) 
could be a potential bioactive metabolite of PPGs since HYD, in equimolar 
amounts to PGGs, is able to both activate HO-1 transcription and modify 
Nrf2/Bach1 nuclear protein levels. This is in agreement with the poor activity 
of CP, which contains a HYD moiety modified by an O-methyl group. In conclusion, 
FB and EC from plant cell cultures may provide long-lasting skin protection by 
induction of phase II cytoprotective capabilities.