Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2017, Article ID 9719647, 10 pages
https://doi.org/10.1155/2017/9719647
Research Article

Glycyrrhizin Protects Rats from Sepsis by Blocking HMGB1 Signaling

Department of Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China

Correspondence should be addressed to Wei Wang; moc.621@7303iewgnawrd

Received 11 January 2017; Revised 28 February 2017; Accepted 12 March 2017; Published 18 April 2017

Academic Editor: Bo Zuo

Copyright © 2017 Feng Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. HMGB1 acts as an important inflammatory mediator and is a potential therapeutic target for sepsis. Glycyrrhizin (GL), a natural triterpene glycoside derived from licorice, has been demonstrated to inhibit HMGB1 activity. The aim of this study is to explore how GL affects the HMGB1 signaling in sepsis. Methods. We used a CLP model of sepsis and in vitro LPS or HMGB1-treated NR8383 cells to examine the effects of GL on expression of HMGB1 and proinflammatory cytokines. Furthermore, we explored the effect of GL on interactions between HMGB1 and RAGE or TLR4 and the activations of NF-κB and MAPKs. Results. GL significantly decreased mortality and reduced serum levels of HMGB1 in vivo. GL also attenuated the release and expression of HMGB1 and proinflammatory cytokines. Direct stimulation by HMGB1 elevated the release of proinflammatory cytokines faster than LPS did and it was also inhibited by GL. Furthermore, GL blocked the interaction of HMGB1 with RAGE and TLR4 and suppressed the downstream MAPKs/NF-κB signaling pathway. Conclusion. GL may protect rats against sepsis by blocking the interaction of HMGB1 with cell surface receptors and HMGB1-mediated inflammatory responses.