An endotoxin inhibitor derived from cinnamon bark was characterized chemically and tested for anti-LPS properties. Chemical analysis suggested that the active center of the inhibitor was in the lipid portion. Upon incubation with LPS molecule, the inhibitor reduced the ability of LPS to induce TNFα and generate nitric oxide from various cells in vitro, and Limulus gelation activity. The lethal toxicity of LPS in galactosamine-sensitized mice and pyrogenicity of LPS in a rabbit model were reduced 1000- and 100-fold by pre-incubation with the inhibitor, respectively. Simultaneous but separate injection of the inhibitor with a lethal dose of LPS also protected the majority of mice. Protection against LPS was seen when the inhibitor was given to mice 1 h before the LPS challenge. Furthermore, the inhibitor significantly suppressed the induction of fever by simultaneous administration with LPS without prior mixing. These results suggest that the inhibitor may be a useful potent blocker of bacterial endotoxin.
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