Escin is an active ingredient used in the treatment of
phlebitis. However, the pharmacological mechanism of
escin remains largely unclear. Here, we aimed to determine the molecular basis for the
therapeutic effect of
escin. Human umbilical vein endothelial cells (HUVECs) were subjected to shear-stress assays with or without
escin. Intracellular Ca2+ levels, inflammatory factors and the activity of NF-κB were measured in endothelial cells (ECs) after mechanical-stretch or Yoda1 activation. Isometric tensions in aortic rings were identified. In addition, murine liver endothelial cells (MLECs) isolated from Piezo1 endothelial specific knockout mice (Piezo1△ EC) were used to explore the role of Piezo1. Our results showed that
escin inhibited inflammatory factors, intracellular Ca2+ levels and Yoda1-evoked relaxation of thoracic aorta rings. Cell alignment induced by shear stress was inhibited by
escin in HUVECs, and Piezo1
siRNA was used to show that this effect was dependent on Piezo1 channels. Moreover,
escin reduced the
inflammation and inhibited the activity of NF-κB in ECs with mechanical-stretch, which were insensitive to Piezo1 deletion. SN50, an NF-κB antagonist, significantly inhibited the mechanical stretch-induced inflammatory response. In addition,
escin reduced
inflammation in ECs subjected to mechanical-stretch, which was insensitive after using NF-κB antagonist. Collectively, our results demonstrate that
escin inhibits the mechanical stretch-induced inflammatory response via a Piezo1-mediated NF-κB pathway. This study improves our understanding of a molecular target of
escin that mediates its effect on chronic vascular
inflammation.