Schisantherin A protects lipopolysaccharide-induced acute respiratory distress syndrome in mice through inhibiting NF-κB and MAPKs signaling pathways.

Abstract

Acute respiratory distress syndrome (ARDS) is characterized by polymorphonuclear neutrophils (PMNs) adhesion, activation, sequestration and inflammatory damage to alveolar-capillary membrane. Schisantherin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been reported to have anti-inflammatory properties. In the present study, we aimed to investigate the protective effects of schisantherin A on LPS-induced mouse ARDS. The pulmonary injury severity was evaluated 7 h after LPS administration and the protective effects of schisantherin A on LPS-induced mouse ARDS were assayed by enzyme-linked immunosorbent assay and Western blot. The results revealed that the wet/dry weight ratio, myeloperoxidase activity, and the number of total cells, neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) were significantly reduced by schisantherin A in a dose-dependent manner. Meanwhile, pretreatment with schisantherin A markedly ameliorated LPS-induced histopathologic changes and decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the BALF. In addition, the phosphorylation of nuclear transcription factor-kappaB (NF-κB) p65, inhibitory kappa B alpha (IκB-α), c-jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 induced by LPS were suppressed by schisantherin A. These findings indicated that schisantherin A exerted potent anti-inflammatory properties in LPS-induced mouse ARDS, possibly through blocking the activation of NF-KB and mitogen activated protein kinases (MAPKs) signaling pathways. Therefore, schisantherin A may be a potential agent for the prophylaxis of ARDS.

• Authors: Ershun Zhou, Yimeng Li, Zhengkai Wei, Yunhe Fu, He Lei, Naisheng Zhang, Zhengtao Yang, Guanghong Xie
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 22 Issue 1 Pg. 133-40 (Sep 2014) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 24975658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cyclooctanes
• Cytokines
• Dioxoles
• Lignans
• Lipopolysaccharides
• NF-kappa B
• Plant Extracts
• schizandrer A
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Cyclooctanes (therapeutic use)
• Cytokines (metabolism)
• Dioxoles (therapeutic use)
• Fruit
• Humans
• Lignans (therapeutic use)
• Lipopolysaccharides (immunology)
• Lung (drug effects, metabolism, pathology)
• Macrophages, Alveolar (drug effects, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• NF-kappa B (metabolism)
• Neutrophils (drug effects, immunology)
• Phytotherapy
• Plant Extracts
• Respiratory Distress Syndrome (drug therapy, immunology)
• Schisandra (immunology)
• Signal Transduction (drug effects)