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Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models

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Author(s)
Hyun-Shik LeeKyoung-jin MinTaeg Kyu KwonJong-Sup BaeWonhwa LeeTae Hoon KimSae-Kwang Ku
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Toxicology and Applied Pharmacology
Issued Date
2012
Volume
262
Issue
1
Keyword
Withaferin AHMGB1EndotheliumInflammationBarrier integrity
Abstract
Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-
inflammatory, cardioactive and central nervous system effects. In this study, we first investigated the possible
barrier protective effects of WFA against pro-inflammatory responses in human umbilical vein endothelial
cells (HUVECs) and in mice induced by high mobility group box 1 protein (HMGB1) and the associated sig-
naling pathways. The barrier protective activities of WFA were determined by measuring permeability, leu-
kocytes adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs.
We found that WFA inhibited lipopolysaccharide (LPS)-induced HMGB1 release and HMGB1-mediated
barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration
of leukocytes to human endothelial cells. WFA also suppressed acetic acid-induced hyperpermeability and
carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed thatWFA suppressed
the production of interleukin 6, tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB)
by HMGB1. Collectively, these results suggest that WFA protects vascular barrier integrity by inhibiting
hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its useful-
ness as a therapy for vascular inflammatory diseases.
© 2012 Elsevier Inc. All rights reserved. Keywords:
Withaferin A
HMGB1
Endothelium
Inflammation
Barrier integrity
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Hyun-Shik Lee et al. (2012). Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models. Toxicology and Applied Pharmacology, 262(1), 91–98. doi: 10.1016/j.taap.2012.04.025
Type
Article
ISSN
0041-008X
Source
https://www.sciencedirect.com/science/article/pii/S0041008X1200172X?via%3Dihub
DOI
10.1016/j.taap.2012.04.025
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34662
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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