p-Synephrine suppresses lipopolysaccharide-induced acute lung injury by inhibition of the NF-κB signaling pathway

Inflamm Res. 2014 Jun;63(6):429-39. doi: 10.1007/s00011-014-0715-7. Epub 2014 Feb 1.

Abstract

Objective: We investigated whether p-synephrine exerts potent anti-inflammatory effects against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo, and we further investigated the inhibitory mechanism of p-synephrine in LPS-induced ALI.

Methods: Lipopolysaccharide (0.5 mg/kg) was instilled intranasally in phosphate-buffered saline to induce acute lung injury, and 6, 24, and 48 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator. We also evaluated the effects of p-synephrine on LPS-induced the severity of pulmonary injury. The phosphorylation of nuclear factor-κB (NF-κB) p65 protein was analyzed by Western blotting.

Results: Our data showed that p-synephrine significantly reduced the amount of inflammatory cells, the lung wet-to-dry weight (W/D) ratio, reactive oxygen species, myeloperoxidase activity and enhanced superoxide dismutase (SOD) in mice with LPS-induced ALI. Tumor necrosis factor α and interleukin (IL)-6 concentrations decreased significantly while the concentration of IL-10 was significantly increased after p-synephrine pretreatment. In addition, p-synephrine suppressed not only the phosphorylation of NF-κB but also the degradation of its inhibitor (IκBα).

Conclusions: These results suggested that the inhibition of NF-κB activation and the regulation of SOD are involved in the mechanism of p-synephrine's protection against ALI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy
  • Acute Lung Injury / immunology*
  • Acute Lung Injury / pathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Count
  • Interleukin-10 / immunology
  • Interleukin-6 / immunology
  • Lipopolysaccharides
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Male
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / immunology
  • Peroxidase / immunology
  • Reactive Oxygen Species / immunology
  • Superoxide Dismutase / immunology
  • Synephrine / pharmacology*
  • Synephrine / therapeutic use
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • IL10 protein, mouse
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Peroxidase
  • Superoxide Dismutase
  • Synephrine