Escin Activates Canonical Wnt/β-Catenin Signaling Pathway by Facilitating the Proteasomal Degradation of Glycogen Synthase Kinase-3β in Cultured Human Dermal Papilla Cells

Abnormal inactivation of the Wnt/β-catenin signaling pathway is involved in skin diseases like androgenetic alopecia, vitiligo and canities, but small-molecule activators are rarely described. In this study, we investigated stimulatory effects escin on canonical cultured human dermal papilla cells (hDPCs). Escin stimulated signaling, resulting increased β-catenin lymphoid enhancer-binding factor 1 (LEF1), accumulation nuclear enhanced expression Wnt target genes hDPCs. drastically reduced protein level glycogen synthase kinase (GSK)-3β, a key regulator pathway, while presence proteasome inhibitor MG-132 fully restored GSK-3β level. The treatment secreted frizzled-related proteins (sFRPs) 2 attenuated activity reporter assays. Our data demonstrate that natural agonist downregulates by facilitating proteasomal degradation suggest likely stimulates through direct interactions with frizzled receptors. This study underscores therapeutic potential for Wnt-related such as canities.