DCE and CS show an inhibitory action on a number of signal transduction pathways, among which STAT3, Flunarizine 2HCl whereas activate many MAP kinases, such as JNK, ERK2 and p38. At molecular level, DCE and CS directly interact with GSH, thereby triggering S-glutathionylation of STAT3 and other substrates. This event leads to a reduced STAT3 tyrosine phosphorylation and activation in response to the inducing cytokine IL-6. Concomitantly to STAT3, the tyrosine Janus kinase 1, JAK2 and Tyk2 are also de-phosphorylated in presence of DCE and CS. In the present study, we hypothesized that the mild oxidative stress induced by DCE and CS treatments regulate inflammatory, Glycopyrrolate proliferative and apoptotic responses of keratinocytes to inflammatory cytokines or in basal conditions. We found that these two terpenes substantially inhibited STAT3 and STAT1 pathways in keratinocytes, whereas enhance EGFR and ERK1/2 activation. DCE and CS decreased the expression of genes involved in cellcycle progression and proliferation, and, in parallel, induced apoptosis and mitosis-arrest of keratinocytes. Interestingly, DCE and CS promoted wound healing in an in vitro injury model by enhancing keratinocyte migratory capabilities. In recent years, a number of effective treatments used for the therapy of psoriasis and based on the increase of local oxidative stress has become attractive. These pro-oxidant treatments activate anti-proliferative and pro-apoptotic pathways in hyperproliferating keratinocytes, thus, counteracting the effects of inflammatory cytokines locally released by infiltrating leukocytes. With the aim at identifying new therapeutic molecules for skin disorders characterized by epidermal hyperproliferation, inflammation and marked resistance to apoptosis, in particular psoriasis, we examined the effects of two plant-derived pro-oxidant molecules, the sesquiterpene lactones DCE and CS, on regulating proliferative, immune, and apoptotic responses of human keratinocytes to inflammatory cytokines or in basal conditions.Previous studies demonstrated that the pro-oxidant effects of DCE and CS were correlated to their direct interaction with GSH that induces a rapid drop in intracellular GSH concentration.