Xin Liu
Third Military Medical University, China
Title: Kukoamine B Ameliorates Rodent Polymicrobial Sepsis via Simultaneous Blockade of Primary PAMPs and Induced Inflammatory Disorderss
Biography
Biography: Xin Liu
Abstract
Kukoamine B (KB) is a alkaloid compound isolated from the traditional Chinese herb Cortex Lycii. KB has been identified as a novel dual antagonist for LPS and CpG DNA, two major pathogen associated molecular patterns (PAMPs) for triggering sepsis. However, its inhibitory effects against LPS and CpG DNA in vivo and the potential therapeutic implications in treating sepsis needs to be well elucidated. In this study, the impact of KB on survivals of different rodent sepsis models was analyzed. Organ distribution and clearance of LPS and CpG DNA in the presence of KB were detected. The antagonistic effects of KB against LPS and CpG DNA, including inflammatory associated cytokines production, coagulation parameters, major organ functions were evaluated in rats CLP model. We found that KB could bind bacterial LPS from different bacterial origins and inhibit the induced release of pro inflammatory cytokines. KB attenuates the activity of LPS and CpG DNA in vivo, accelerates their circulatory clearance and increases liver uptake. KB effectively improves the survival of different murine sepsis models. KB also ameliorates the production of pro- and anti-inflammatory cytokines and serum biomarkers of sepsis in CLP rats. KB is efficacy in reversing their acidosis state, suppressing DIC and organ dysfunctions and limiting acute lung injuries secondary to sepsis. Overall, KB is effective in simultaneously blockade of LPS and CpG DNA in vivo and improves the outcomes in rodent sepsis models. KB may become a promising candidate drug for the treatment of sepsis.