Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

Abstract

Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis.

• Authors: Qi Sun, Ling Chen, Mengyu Gao, Wenwen Jiang, Fangxian Shao, Jingjing Li, Jun Wang, Junping Kou, Boyang Yu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 12 Issue 1 Pg. 88-93 (Jan 2012) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 22079591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Lipopolysaccharides
• NF-kappa B
• Nitrates
• Nitrites
• Spirostans
• Thromboplastin
• ruscogenin
• Peroxidase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Acute Lung Injury (chemically induced, drug therapy, metabolism, pathology)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Disease Models, Animal
• Lipopolysaccharides
• Male
• Mice
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Nitrates (blood)
• Nitric Oxide Synthase Type II (metabolism)
• Nitrites (blood)
• Peroxidase (metabolism)
• Spirostans (pharmacology, therapeutic use)
• Thromboplastin (metabolism)