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Title: Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice

Abstract

High mobility group box 1 (HMGB1) is considered a late mediator of sepsis and the inhibition of HMGB1-mediated severe inflammatory responses and restoration of endothelial integrity have emerged as attractive therapeutic strategies for the management of sepsis. Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess various pharmacological activities. We examined the effects of ZGR on HMGB1-mediated septic responses and survival rate in a mouse model of sepsis. ZGR was administered after HMGB1 challenge. The antiseptic activity of ZGR was determined from the measurements of permeability, leukocyte adhesion and migration, activation of pro-inflammatory proteins, and the production of tissue injury markers in HMGB1-activated HUVECs and mice. ZGR significantly reduced HMGB1 release in LPS-activated HUVECs via the SIRT1-mediated deacetylation of HMGB1. And, ZGR suppressed the production of TNF-α and IL-6 and the activation of NF-κB and ERK 1/2 by HMGB1. ZGR also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with ZGR reduced the CLP-induced release of HMGB1, sepsis-related mortality, and tissue injury in vivo. Our results indicated that ZGR might be useful in the treatment of sepsis by targeting HMGB1. - Highlights: • HMGB1 is considered a late mediator of sepsis. • Zingeronemore » suppressed LPS-induced secretion of HMGB1 in vitro and in vivo. • Zingerone reduced HMGB1-mediated hyperpermeability in vitro and in vivo. • Zingerone inhibited HMGB1-mediated leukocytes adhesion and migration. • Zingerone reduced mortality and lung injury in mouse sepsis model.« less

Authors:
 [1];  [2];  [1]
  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 (Korea, Republic of)
  2. Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22722898
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 329; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL RECOVERY; INHIBITION; INJURIES; LEUKOCYTES; MICE; MIGRATION

Citation Formats

Lee, Wonhwa, Ku, Sae-Kwang, and Bae, Jong-Sup. Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.06.006.
Lee, Wonhwa, Ku, Sae-Kwang, & Bae, Jong-Sup. Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice. United States. doi:10.1016/J.TAAP.2017.06.006.
Lee, Wonhwa, Ku, Sae-Kwang, and Bae, Jong-Sup. Tue . "Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice". United States. doi:10.1016/J.TAAP.2017.06.006.
@article{osti_22722898,
title = {Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice},
author = {Lee, Wonhwa and Ku, Sae-Kwang and Bae, Jong-Sup},
abstractNote = {High mobility group box 1 (HMGB1) is considered a late mediator of sepsis and the inhibition of HMGB1-mediated severe inflammatory responses and restoration of endothelial integrity have emerged as attractive therapeutic strategies for the management of sepsis. Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess various pharmacological activities. We examined the effects of ZGR on HMGB1-mediated septic responses and survival rate in a mouse model of sepsis. ZGR was administered after HMGB1 challenge. The antiseptic activity of ZGR was determined from the measurements of permeability, leukocyte adhesion and migration, activation of pro-inflammatory proteins, and the production of tissue injury markers in HMGB1-activated HUVECs and mice. ZGR significantly reduced HMGB1 release in LPS-activated HUVECs via the SIRT1-mediated deacetylation of HMGB1. And, ZGR suppressed the production of TNF-α and IL-6 and the activation of NF-κB and ERK 1/2 by HMGB1. ZGR also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with ZGR reduced the CLP-induced release of HMGB1, sepsis-related mortality, and tissue injury in vivo. Our results indicated that ZGR might be useful in the treatment of sepsis by targeting HMGB1. - Highlights: • HMGB1 is considered a late mediator of sepsis. • Zingerone suppressed LPS-induced secretion of HMGB1 in vitro and in vivo. • Zingerone reduced HMGB1-mediated hyperpermeability in vitro and in vivo. • Zingerone inhibited HMGB1-mediated leukocytes adhesion and migration. • Zingerone reduced mortality and lung injury in mouse sepsis model.},
doi = {10.1016/J.TAAP.2017.06.006},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 329,
place = {United States},
year = {2017},
month = {8}
}