Shikonin ameliorates lipoteichoic acid‑induced acute lung injury via promotion of neutrophil apoptosis

Mol Med Rep. 2021 Feb;23(2):133. doi: 10.3892/mmr.2020.11772. Epub 2020 Dec 14.

Abstract

Shikonin is the major active component in Lithospermum erythrorhizon and has pharmacological effects including reducing inflammation, aiding resistance to bacteria and promoting wound healing. However, the effect of shikonin on lipoteichoic acid (LTA)‑induced acute lung injury (ALI) remains to be elucidated. ALI is a serious illness resulting from significant pulmonary inflammation caused by various diseases, such as sepsis, acid aspiration and trauma. The present study found that shikonin significantly attenuated LTA‑induced ALI. Following shikonin treatment, the accumulation of pulmonary neutrophils and expression of TNFα, IL‑1β and IL‑6 were decreased in mice with LTA‑induced ALI. Furthermore, Shikonin promoted neutrophil apoptosis by increasing the activation of caspase‑3 and reducing the expression of the antiapoptotic myeloid cell leukemia‑1 (Mcl‑1) protein. However, shikonin treatment did not influence the expression of B‑cell lymphoma‑2. The findings of the present study demonstrated that shikonin protected against LTA‑induced ALI by promoting caspase-3 and Mcl‑1‑related neutrophil apoptosis, suggesting that shikonin is a potential agent that can be used in the treatment of sepsis‑mediated lung injury.

Keywords: shikonin; lipoteichoic acid; acute lung injury; neutrophil; apoptosis; myeloid cell leukemia‑1.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / pathology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Apoptosis / drug effects
  • Bronchoalveolar Lavage Fluid / chemistry
  • Caspase 3 / metabolism
  • Cytokines / metabolism
  • DNA Fragmentation / drug effects
  • Disease Models, Animal
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Naphthoquinones / pharmacology*
  • Naphthoquinones / therapeutic use
  • Neutrophil Infiltration / drug effects
  • Neutrophils / cytology*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Teichoic Acids / toxicity
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Lipopolysaccharides
  • Mcl1 protein, mouse
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Naphthoquinones
  • Teichoic Acids
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • shikonin
  • lipoteichoic acid
  • Poly(ADP-ribose) Polymerases
  • Casp3 protein, mouse
  • Caspase 3