Objective        To observe the in vitro and in vivo pharmacological antagonistic activity of kukoamine B (KB) on sepsis.       Methods        Affinity of KB to lipopolysaccharide (LPS) and CpG DNA in E.coli was detected by dual polarization interferometry

in vitro ability of KB to neutralize LPS in E.coli was assayed by limulus amebocyte lysate (LAL) test

and inhibitory effect of KB on release of TNF-α and IL-6 from RAW 264.7 cells induced by either LPS and CpG DNA alone or by heat-inactivated E.coli and Staphylococcus aureus was detected by ELISA. A mouse sepsis model was induced by injecting heat-inactivated E.coli and Staphylococcus aureus into abdominal cavity of BALB/c mice. The BALB/c mice divided into control group

low dose KB group

medium KB dose group

high KB dose group

and clinical drug treatment group with their mortality observed for 7 days and compared.       Results        The affinity of KB to LPS and CpG ODN1826 was 7.38 and 197.2 nmol/L

respectively. KB significantly inhibited the in vitro coagulation effect of KB on LPS (P0.05 or P0.01) and the release of TNF-α and IL-6 from RAW 264.7 cells induced by heat-inactivated E.coli and Staphylococcus aureus in a dose-dependent manner. KB played a significant role in protecting mice against severe and extremely severe sepsis. The survival rate of mice was significantly higher in KB group than in control group and clinical drug treatment group (P0.05 or P0.01).       Conclusion        KB

as a neutralizer of several pathogen molecules，can inhibit the release of inflammatory cytokines and plays a role in protecting mice against sepsis. Its effect is significantly better than that of Xuebijing and ulinastatin.