Anti-vascular inflammatory effects of pentacyclic triterpenoids from Astilbe rivularis in vitro and in vivo

作者:Kang, Hyejin; Ku, Sae-Kwang; Kim, Jongdoo; Chung, Jiwoo; Kim, Sang Chan; Zhou, Wei; Na, MinKyun*; Bae, Jong-Sup*
来源:Chemico-Biological Interactions, 2017, 261: 127-138.
DOI:10.1016/j.cbi.2016.11.014

摘要

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 b induced protein (TGFBIp) is an extracellular matrix protein that functions as a mediator of experimental sepsis. C-27carboxylated 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 3b-trans-p-coumaroyloxy-olean-12-en-27-oic acid (1) and 6b-hydroxy-3-oxoolean12- 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 antiinflammatory functions by inhibiting hyperpermeability, CAM expression, and leukocyte adhesion/migration. Therefore, these compounds can be considered as a potential therapy for vascular inflammatory diseases.