Anti-Septic Effects of Cudratricusxanthone A Against HMGB1-Mediated Septic Responses

Abstract

Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the roots of Cudrania tricuspidata Bureau, is known to possess hepatoprotective, antiproliferative, and anti-inflammatory activities. Inhibition of high-mobility group box 1 (HMGB1) and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of severe sepsis or septic shock. Here, we examined the effects of CTXA on HMGB1-mediated barrier disruptive responses and survival rate in a mouse sepsis model. The anti-inflammatory activities of CTXA were monitored by the effects on lipopolysaccharide-or cecal ligation and puncture (CLP)-mediated release of HMGB1. In addition, treatment with CTXA reduced CLP-induced mouse mortality in vivo. Our results indicate that CTXA could be a candidate for a therapeutic agent for various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.