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Chem Biol Interact. 2016 Jul 25;254:179-90. doi: 10.1016/j.cbi.2016.06.015. Epub 2016 Jun 7.

Inhibitory effects of pentacyclic triterpenoids from Astilbe rivularis on TGFBIp-induced inflammatory responses in vitro and in vivo.

Author information

1
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.
2
College of Pharmacy, Yanbian University, Yanji 133002, People's Republic of China.
3
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea. Electronic address: mkna@cnu.ac.kr.
4
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: baejs@knu.ac.kr.

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.

KEYWORDS:

Astilbe rivularis; Inflammation; Pentacyclic triterpenoids; Sepsis; TGFBIp

PMID:
27287417
DOI:
10.1016/j.cbi.2016.06.015
[Indexed for MEDLINE]

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