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Title: Vascular barrier protective effects of baicalin, baicalein and wogonin in vitro and in vivo

Inhibition of high mobility group box 1 (HMGB1) protein and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of sepsis. Here, three structurally related polyphenols found in the Chinese herb Huang Qui, baicalin (BCL), baicalein (BCN), and wogonin (WGN), were examined for their effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. According to our data, BCL, BCN, and WGN inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. BCL, BCN, and WGN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with BCL, BCN, and WGN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that BCL, BCN, and WGN could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway. - Highlights: • HMGB1 is an inflammatory mediator for vascular inflammation. • Baicalin, baicalein and wogonin inhibited HMGB1-induced hyperpermeability in vitro and in vivo. • Baicalin, baicalein and wogonin inhibited HMGB1-mediated inflammatory responses. • Baicalin, baicalein and wogonin suppressed the activation of NF-κB and ERK1/2 and productionmore » of TNF-α and IL-6. • Baicalin, baicalein and wogonin prevent CLP-induced septic mortality.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1]
  1. College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)
  2. Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715 (Korea, Republic of)
  3. Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Fatima Hospital, Daegu 701-600 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22439906
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 281; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADHESION; CHINA; DRUGS; ENZYME IMMUNOASSAY; ENZYMES; HERBS; IN VITRO; IN VIVO; INFLAMMATION; INJURIES; LEUKOCYTES; MICE; MORTALITY; RECEPTORS