Glycyrrhizin inhibits traumatic brain injury by reducing HMGB1-RAGE interaction

Yu Okuma, Keyue Liu, Hidenori Wake, Rui Liu, Yoshito Nishimura, Zhong Hui, Kiyoshi Teshigawara, Jun Haruma, Yasuhiko Yamamoto, Hiroshi Yamamoto, Isao Date, Hideo K. Takahashi, Shuji Mori, Masahiro Nishibori

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)


Glycyrrhizin (GL) is a major constituent of licorice root and has been suggested to inhibit the release of high mobility group box-1 (HMGB1), a protein considered representative of damage-associated molecular patterns. We found that GL bound HMGB1 but not RAGE with a moderate equilibrium dissociation constant value based on surface plasmon resonance analysis. This complex formation prevented HMGB1 from binding to RAGE in vitro. The effects of glycyrrhizin on traumatic brain injury (TBI) induced by fluid percussion were examined in rats or mice in the present study. GL was administered intravenously after TBI. Treatment of rats with GL dose-dependently suppressed the increase in BBB permeability and impairment of motor functions, in association with the inhibition of HMGB1 translocation in neurons in injured sites. The beneficial effects of GL on motor and cognitive functions persisted for 7 days after injury. The expression of TNF-α, IL-1β and IL-6 in injured sites was completely inhibited by GL treatment. In RAGE-/- mice, the effects of GL were not observed. These results suggested that GL may be a novel therapeutic agent for TBI through its interference with HMGB1 and RAGE interaction.

Original languageEnglish
Pages (from-to)18-26
Number of pages9
Publication statusPublished - Oct 2014


  • Brain edema
  • Glycyrrhizin
  • HMGB1
  • RAGE
  • Traumatic brain injury

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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