Shikonin exerts anti-inflammatory effects in a murine model of lipopolysaccharide-induced acute lung injury by inhibiting the nuclear factor-kappaB signaling pathway

Int Immunopharmacol. 2013 Aug;16(4):475-80. doi: 10.1016/j.intimp.2013.04.020. Epub 2013 May 4.

Abstract

Shikonin, an analog of naphthoquinone pigments isolated from the root of Lithospermum erythrorhyzon, was recently reported to exert beneficial anti-inflammatory effects both in vivo and in vitro. The present study aimed to investigate the potential therapeutic effect of shikonin in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Dexamethasone was used as a positive control to evaluate the anti-inflammatory effect of shikonin in the study. Pretreatment with shikonin (intraperitoneal injection) significantly inhibited LPS-induced increases in the macrophage and neutrophil infiltration of lung tissues and markedly attenuated myeloperoxidase activity. Furthermore, shikonin significantly reduced the concentrations of TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid induced by LPS. Compared with the LPS group, lung histopathologic changes were less pronounced in the shikonin-pretreated mice. Additionally, Western blotting results showed that shikonin efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that shikonin exerts anti-inflammatory properties in LPS-mediated ALI, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. Shikonin may be a potential agent for the prophylaxis of 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
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / immunology
  • Disease Models, Animal
  • Lipopolysaccharides / toxicity*
  • Lithospermum / chemistry
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors*
  • Naphthoquinones / administration & dosage
  • Naphthoquinones / isolation & purification
  • Naphthoquinones / therapeutic use*
  • Organ Size / drug effects
  • Plant Roots / chemistry
  • Signal Transduction / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Naphthoquinones
  • lipopolysaccharide, E coli O55-B5
  • shikonin