Emodin-6-O-β-d-glucoside inhibits HMGB1-induced inflammatory responses in vitro and in vivo

High mobility group box 1 (HMGB1) protein acts as a potent proinflammatory cytokine and is involved in the pathogenesis of several vascular diseases, such as, systemic vasculitis and sepsis. Emodin-6-O-β-d-glucoside (EG) is a new active compound from Reynoutria japonica, and its biologic activities have not been previously investigated. In this study, we first investigated the antiinflammatory activities of EG on HMGB1-mediated proinflammatory responses in human umbilical vein endothelial cells (HUVECs) and in a murine cecal ligation and puncture (CLP)-model of sepsis in mice. EG was found to suppress the release of HMGB1, the production of tumor necrosis factor (TNF)-α, and the activation of nuclear factor-κB (NF-κB) by HMGB1 in HUVECs, and to inhibit HMGB1-mediated hyperpermeability and leukocyte migration in mice. In the CLP model, HMGB1 was highly released, but this release was prevented by EG. Furthermore, EG also increased the survival times of CLP administered mice. Collectively, this study shows EG can protect barrier integrity and inhibit HMGB1-mediated inflammatory responses, which suggests a potential use as a therapy for sepsis or septic shock.