Microcirculation-Promoting Effect of Escin on Cutaneous Tissue via Gsk3β Down-Regulation

Microcirculation in cutaneous tissue is essential to balance oxygen delivery and maintain the health of the skin. Senescence contributes to microcirculatory dysfunction through mechanisms involving chronic inflammation, structural remodeling of microvessels, and disturbances in hemodynamics. In this study we investigated the promoting effect of escin on blood flow through topical application. To elucidate the molecular mechanisms of escin, kinase phosphorylation changes in human umbilical vein endothelial cells (HUVECs) were examined. Escin stimulates the Wnt/β-Catenin and c-Jun N-terminal kinase (JNK) signaling pathway in cultured HUVECs. To clarify the target of escin in the Wnt/β-Catenin signaling pathway, gene expression in response to escin treatment was evaluated, and escin-mediated signaling activation was accompanied by glycogen synthase kinase-3 beta (Gsk3β), according to inhibitor studies performed with IWR1 (tankyrase inhibitor). In addition, the expression level of the Gsk3β were down-regulated by escin treatment in cultured HUEVCs. Escin also enhanced vascular remodeling, and, when applied topically, led to a sustained increase in cutaneous blood flow. Escin-mediated Wnt signaling activation could enhance blood vessel networks via Gsk3β down-regulation. In conclusion, our data demonstrate that escin promotes angiogenic behavior and enhances adenosine-induced perfusion in humans, thereby supporting its potential role in modulating cutaneous microcirculation.