Forsythoside B Protects Against Experimental Sepsis by Modulating Inflammatory Factors

The present study investigated the effects of Forsythoside B on an experimental model of sepsis induced by caecal ligation and puncture (CLP) in rats and elucidated the potential mechanism in cultured RAW 264.7 cells. Results showed that Forsythoside B concentration‐dependently down‐regulated the levels of TNF‐α, IL‐6 and high‐mobility group‐box 1 protein (HMGB1) in lipopolysaccharide (LPS)‐stimulated RAW264.7 cells, inhibited the IκB kinase (IKK) pathway and modulated nuclear factor (NF)‐ κB. Intravenous injection (i.v.) of Forsythoside B alone or plus Imipenem reduced serum levels of TNF‐α, IL‐6, HMGB1, triggering receptor expressed on myeloid cells (TREM‐1) and endotoxin, while the serum level of IL‐10 was up‐regulated and myeloperoxidase (MPO) in lung, liver and small intestine was reduced. Meanwhile, i.v. of Forsythoside B alone or plus Imipenem reduced CLP‐induced lethality in rats. These data indicated that the antisepsis effect of Forsythoside B is mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. Its antisepsis mechanism may be that Forsythoside B binds to LPS and reduces the biological activity of serum LPS, and inhibits NF‐κB activition. Our studies enhance the case for the use of Forsythoside B in sepsis. Forsythoside B itself has promise as a therapy for the treatment of sepsis in humans. Copyright © 2011 John Wiley & Sons, Ltd.