Abstract
Sepsis is a systemic inflammatory condition resulting from bacterial infections. It is associated with high mortality rates, and its therapeutic options are limited. Transforming growth factor β induced protein (TGFBIp) is an extracellular matrix protein that functions as a mediator of experimental sepsis. C-27-carboxylated pentacyclic triterpenoids are specifically found in species of the genus Astilbe, and show several biological effects. Given the anti-inflammatory effects of pentacyclic triterpenoids, we investigated the effects of 3β-trans-p-coumaroyloxy-olean-12-en-27-oic acid (1) and 6β-hydroxy-3-oxoolean-12-en-27-oic acid (2) on TGFBIp-mediated vascular inflammatory responses. The anti-inflammatory activities of compounds 1 and 2 were determined by measuring the permeability, leukocyte adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated human umbilical vein endothelial cells (HUVECs) and mice. We found that compounds 1 and 2 inhibited lipopolysaccharide (LPS)-induced TGFBIp secretion, TGFBIp-induced barrier disruption, expression of cell adhesion molecules (CAMs), and the adhesion/transendothelial migration of the neutrophils to the human endothelial cells. Compounds 1 and 2 also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo. These results suggested that C-27-carboxylated pentacyclic triterpenoids 1 and 2 have anti-inflammatory functions by inhibiting hyperpermeability, CAM expression, and leukocyte adhesion/migration. Therefore, these compounds can be considered as a potential therapy for vascular inflammatory diseases.