1. Inhibitory effects of pentacyclic triterpenoids from Astilbe rivularis on TGFBIp-induced inflammatory responses in vitro and in vivo.
- Author
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Jung B, Chung J, Zhou W, Lee T, Na M, and Bae JS
- Subjects
- Alanine Transaminase blood, Animals, Anti-Inflammatory Agents therapeutic use, Aspartate Aminotransferases blood, Cell Movement drug effects, Cell Survival drug effects, Extracellular Matrix Proteins genetics, Extracellular Matrix Proteins metabolism, HMGB1 Protein metabolism, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism, Humans, Integrin beta Chains chemistry, Integrin beta Chains genetics, Integrin beta Chains metabolism, Male, Mice, Mice, Inbred C57BL, Oleanolic Acid chemistry, Oleanolic Acid pharmacology, Oleanolic Acid therapeutic use, Permeability drug effects, RNA, Small Interfering metabolism, Saxifragaceae metabolism, Sepsis drug therapy, Sepsis etiology, Sepsis metabolism, Transforming Growth Factor beta genetics, Transforming Growth Factor beta metabolism, Triterpenes chemistry, Triterpenes therapeutic use, Vascular Cell Adhesion Molecule-1 metabolism, Anti-Inflammatory Agents pharmacology, Cell Adhesion drug effects, Extracellular Matrix Proteins analysis, Oleanolic Acid analogs & derivatives, Saxifragaceae chemistry, Transforming Growth Factor beta analysis, Triterpenes pharmacology
- Abstract
Transforming growth factor β induced protein (TGFBIp) is an extracellular matrix protein which expression in several cell types is greatly increased by TGF-β. TGFBIp is released by human umbilical vein endothelial cells (HUVECs), and functions as a mediator of experimental sepsis. Pentacyclic triterpenoids bearing a carboxyl group at C-27 position, 3β,6α-dihydroxyolup-20(29)-ene (1), 3β,6β-dihydroxyolean-12-en-27-oic acid (2) and 3β,24-dihydroxyolean-12-en-27-oic acid (3), are representative bioactive molecules in the genus Astilbe that possess cytotoxic, anti-inflammatory and wounds healing activities. Based on the biological effects of C-27 carboxylated pentacyclic triterpenoids, we investigated the anti-inflammatory effects of compounds 1-3 against TGFBIp-mediated vascular inflammatory responses. The anti-inflammatory activities of compounds 1-3 were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated human HUVECs and mice. We found that compounds 1-3 inhibited TGFBIp-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of neutrophils to human endothelial cells. Each compound also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo. These results suggest that compounds 1-3 possess anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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