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.
Copyright Georg Thieme Verlag KG Stuttgart. New York.