This study was conducted to investigate the efficacy of
cornuside, a
secoiridoid glucoside compound, in cultured macrophages as well as in an experimental model of
sepsis induced by cecal
ligation and
puncture (CLP) in rats.
Cornuside was added to cultured macrophages at different concentrations, and all CLP rats were randomized to receive an
intravenous injection of the corresponding
drug followed by observation of its antisepsis effect. Our results showed that
cornuside downregulated the levels of
TNF- alpha,
IL-6, and NO production in a dose-dependent manner in activated macrophages, while it upregulated the level of
IL-10.
Intravenous injection of
cornuside or
imipenem alone or in combination reduced CLP-induced lethality in rats after CLP. In addition, serum levels of
TNF- alpha,
IL-6, triggering receptor expressed on myeloid cells, and
endotoxin were downregulated. On the other hand, the serum levels of
IL-10 were upregulated. Decreased bacterial counts in blood, peritoneum, spleen, liver, and mesenteric lymph nodes and decreased
myeloperoxidase in lung, liver, and small intestine also were found after
cornuside injection. These data indicate that the antisepsis
therapeutic effect of
cornuside is mediated by decreased local and systemic levels of a wide spectrum of inflammatory mediators. This work provides first evidence for the clinic use of
cornuside as a new immunomodulatory
drug that has the capacity to inhibit the inflammatory response in
sepsis.