Esculin attenuates endotoxin shock induced by lipopolysaccharide in mouse and NO production in vitro through inhibition of NF-κB activation.

Abstract

Esculin, a coumarin compound derived from the traditional Chinese herbs such as Cortex Fraxini, has long been used for treating inflammatory and vascular diseases. In present study, we analyzed the role of esculin against macrophages and endotoxin shock induced by lipopolysaccharide (LPS) in mice. Here, we demonstrated that esculin suppressed inflammatory reactions in macrophages and protected mice from LPS-induced endotoxin shock. We found that esculin significantly inhibited the production of nitric oxide (NO) production via the inhibition of nuclear factor-κB (NF-κB) activation in macrophages. In animal model, esculin pretreatment significantly improved the survival rate of mice. LPS-induced increase of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in serum, lung, liver and kidney were markedly inhibited by esculin. IL-10, an anti-inflammatory cytokine, was up-regulated by esculin. Moreover, the histopathological analyses showed that esculin significantly attenuated the tissues injury of lung, liver, kidney in endotoxic mice. In addition, esculin significantly diminished the protein expression of NF-κB p65 in lung, liver, kidney, which resulted in lower levels of inflammatory mediators. These results suggest that esculin may be a potential drug for treatment of various inflammatory diseases.

• Authors: Weifeng Li, Yu Wang, Xiumei Wang, Zehong He, Fang Liu, Wenbing Zhi, Hailin Zhang, Xiaofeng Niu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 791 Pg. 726-734 (Nov 15 2016) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 27746168 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-6
• Lipopolysaccharides
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Esculin
• Nitric Oxide

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Esculin (pharmacology, therapeutic use)
• Female
• Gene Expression Regulation (drug effects)
• Interleukin-10 (blood)
• Interleukin-6 (biosynthesis, blood)
• Lipopolysaccharides (toxicity)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Nitric Oxide (biosynthesis, blood)
• Organ Specificity
• Shock, Septic (chemically induced, drug therapy, metabolism)
• Transcription Factor RelA (metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis, blood)