Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice
- 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)
- Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610 (Korea, Republic of)
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.
- OSTI ID:
- 22722898
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 329; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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