Forsythoside B protects against experimental sepsis by modulating inflammatory factors.

Abstract

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.

• Authors: Wang-Lin Jiang, Yong-Xu, Shu-Ping Zhang, Hai-Bo Zhu, Jian-Hou
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 26 Issue 7 Pg. 981-7 (Jul 2012) ISSN: 1099-1573 [Electronic] England
• PMID: 22147417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Caffeic Acids
• Glucosides
• HMGB1 Protein
• Inflammation Mediators
• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• Receptors, Immunologic
• TREM1 protein, rat
• Triggering Receptor Expressed on Myeloid Cells-1
• Tumor Necrosis Factor-alpha
• forsythoside B
• Interleukin-10
• Imipenem
• Peroxidase
• I-kappa B Kinase

Topics

• Animals
• Caffeic Acids (pharmacology)
• Cell Line
• Glucosides (pharmacology)
• HMGB1 Protein (metabolism)
• I-kappa B Kinase (metabolism)
• Imipenem (pharmacology)
• Inflammation Mediators (metabolism)
• Interleukin-10 (blood)
• Interleukin-6 (metabolism)
• Intestine, Small (drug effects)
• Lipopolysaccharides (pharmacology)
• Liver (drug effects)
• Lung (drug effects)
• Male
• Mice
• NF-kappa B (metabolism)
• Peroxidase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Immunologic (metabolism)
• Sepsis (drug therapy)
• Triggering Receptor Expressed on Myeloid Cells-1
• Tumor Necrosis Factor-alpha (metabolism)