Anti-Septic Functions of Cornuside against HMGB1-Mediated Severe Inflammatory Responses

High mobility group box 1 (HMGB1) is acknowledged to have critical functions; therefore, targeting this protein may have therapeutic effects. One example is potential antiseptic activity obtained by suppressing HMGB1 secretion, leading to the recovery of vascular barrier integrity. Cornuside (CN), which is a product extracted from the fruit of Cornusofficinalis Seib, is a natural bis-iridoid glycoside with the therapeutic effects of suppressing inflammation and regulating immune responses. However, the mechanism of action of CN and impact on sepsis is still unclear. We examined if CN could suppress HMGB1-induced excessive permeability and if the reduction of HMGB1 in response to LPS treatment increased the survival rate in a mouse model of sepsis. In human endothelial cells stimulated by LPS and mice with septic symptoms of cecal ligation and puncture (CLP), we examined levels of proinflammatory proteins and biomarkers as an index of tissue damage, along with decreased vascular permeability. In both LPS-treated human umbilical vein endothelial cells (HUVECs) and the CLP-treated mouse model of sepsis, we applied CN after the induction processes were over. CN suppressed excessive permeability and inhibited HMGB1 release, leading to the amelioration of vascular instability, reduced mortality, and improved histological conditions in the CLP-induced septic mouse model. Overall, we conclude that the suppressed release of HMGB1 and the increased survival rate of mice with CLP-induced sepsis caused by CN may be an effective pharmaceutical treatment for sepsis.