Inhibition Effect of Glycyrrhizin in... : Shock (original) (raw)

Basic Science Aspects

Inhibition Effect of Glycyrrhizin in Lipopolysaccharide-Induced High-Mobility Group Box 1 Releasing and Expression From RAW264.7 Cells

Wu, Chuan-Xin*; He, Lin-Xiang*; Guo, Hui†; Tian, Xiao-Xing†; Liu, Qi†; Sun, Hang†

*Department of Hepatobiliary Surgery and †Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

Received 30 Sep 2014; first review completed 17 Oct 2014; accepted in final form 24 Nov 2014

Address reprint requests to Hang Sun, PhD, MD, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing 400010, China. E-mail: [email protected].

C-X.W. and L-X.H. contributed equally to this study.

This work was supported by a grant from the National Natural Science Foundation of China (no. 81171543) and the Traditional Chinese Medicine Science and Technology Research Project of Chongqing health Bureau (no. 2011-2-120).

Abstract

Introduction

High-mobility group box 1 (HMGB1) is a therapeutic target for sepsis. Glycyrrhizin (GL) is the aglycone of glycyrrhizin derived from licorice. We clarified the anti-inflammatory effects of GL. We explored the anti-HMGB1 effect of GL and elucidated its molecular mechanism, which will be of benefit for sepsis treatment.

Methods

We stimulated murine macrophage-like RAW 264.7 cells with lipopolysaccharide (LPS) and LPS + GL, then measured the expression and release of HMGB1. The expression of related signal transduction factors was detected.

Results

High-mobility group box 1 was distributed mainly in the nucleus with lower cytoplasmic levels in RAW 264.7 cells before LPS stimulation. After stimulation, cytoplasmic HMGB1 levels increased gradually, whereas in nuclear fluctuation a trend of HMGB1 expression was observed. Significant upregulation of HMGB1 mRNA occurred 12 h after LPS stimulation. Glycyrrhizin prevented the transfer of HMGB1 from the nucleus to the cytoplasm and inhibited upregulation of HMGB1 mRNA induced by LPS. Phospho–p38 mitogen-activated protein kinase and activated activating protein 1 increased significantly 8 h after LPS stimulation. Tumor necrosis factor α and interleukin 6 increased 4 h after LPS stimulation and peaked at 48 h, and HMGB1 increased at 8 h. The Toll-like receptor 4/MD2/nuclear factor κB signaling pathway was activated 4 h after LPS stimulation. Glycyrrhizin inhibited this pathway.

Conclusions

Glycyrrhizin inhibited the expression and release of HMGB1 through blocking the p38 mitogen-activated protein kinase/activating protein 1 signaling pathway then inhibited the massive release of tumor necrosis factor α and interleukin 6.