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

Toxicology and Applied Pharmacology
Wonhwa LeeJong-Sup Bae

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 signaling pathways. The barrier protective activities of WFA were determined by measuring permeability, leukocytes 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 that WFA 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...Continue Reading

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Citations

Dec 3, 2013·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Hayoung YooJong-Sup Bae
Jan 29, 2014·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Sae-Kwang KuJong-Sup Bae
Mar 21, 2013·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Sae-Kwang Ku, Jong-Sup Bae
Jan 29, 2013·Toxicology and Applied Pharmacology·Wonhwa LeeJong-Sup Bae
Nov 14, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Wonhwa LeeJong-Sup Bae
Aug 27, 2015·Cellular and Molecular Life Sciences : CMLS·Nawab John DarMuzamil Ahmad
Nov 3, 2015·Journal of Agricultural and Food Chemistry·Nguyen Quoc TuanMinKyun Na
Jul 25, 2015·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Eun-Ju YangJong-Sup Bae
Jul 11, 2014·Molecular Aspects of Medicine·Rui KangDaolin Tang
Mar 19, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Sae-Kwang KuJong-Sup Bae
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Sep 17, 2014·Toxicology and Applied Pharmacology·Soyoung KwakJong-Sup Bae
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Nov 5, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Wonhwa LeeJong-Sup Bae
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Mar 10, 2016·International Journal of Molecular Sciences·In-Chul Lee, Bu Young Choi
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