Solubilization of insoluble glycyrrhizin derivative having anti-HMGB1 effect and its biological activity

Abstract

We have so far investigated the effect of the glycyrrhizin derivatives on high-mobility group box (HMGB)1. We found a glycyrrhizin derivative having potent anti-HMGB1 activity; however, the derivative was very insoluble. In this study, we succeeded in solubilizing the glycyrrhizin derivative. The glycyrrhizin derivative preparation can be injected intravenously and showed higher transition ratio in the brain than p.o. administration in an in vivo murine intracerebral hemorrhage (ICH) model. Intravenous injection of the low-dose (4 mg/kg) glycyrrhizin derivative preparation showed more potent suppression effect on interleukin-1beta mRNA expression than p.o. administration of the suspension of the high-dose (50 mg/kg) glycyrrhizin derivative. Also, intravenous injection of the glycyrrhizin derivative preparation potently suppressed the ICH-induced brain edema. This glycyrrhizin derivative preparation may be a hint for the development of novel ICH treatment medicines.