Protective effect of wogonin on endotoxin-induced acute lung injury via reduction of p38 MAPK and JNK phosphorylation

Environ Toxicol. 2017 Feb;32(2):397-403. doi: 10.1002/tox.22243. Epub 2016 Feb 18.

Abstract

Acute lung injury (ALI) is a serious inflammatory disorder which remains the primary cause of incidence and mortality in patients with acute pulmonary inflammation. However, there is still no effective medical strategy available clinically for the improvement of ALI. Wogonin, isolated from roots of Scutellaria baicalensis Georgi, is a common medicinal herb which presents biological and pharmacological effects, including antioxidation, anti-inflammation, and anticancer. Preadministration of wogonin inhibited not only lung edema but also protein leakage into the alveolar space in murine model of lipopolysaccharide (LPS)-induced ALI. Moreover, wogonin not only reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) induced by LPS. We further found wogonin inhibited the phosphorylation of p38 MAPK and JNK at a concentration lower than ERK. In addition, inhibition of lung edema, protein leakage, expression of iNOS and COX-2, and phosphorylation of p38 MAPK and JNK were all observed in a parallel concentration-dependent manner. These results suggest that wogonin possesses potential protective effect against LPS-induced ALI via downregulation of iNOS and COX-2 expression by blocking phosphorylation of p38 MAPK and JNK. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 397-403, 2017.

Keywords: COX-2; MAPK; acute lung injury; iNOS; wogonin.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / enzymology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Antioxidants / pharmacology*
  • Bronchoalveolar Lavage Fluid
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Endotoxins / antagonists & inhibitors*
  • Endotoxins / toxicity*
  • Flavanones / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Phosphorylation / drug effects
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / prevention & control
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

  • Antioxidants
  • Cyclooxygenase 2 Inhibitors
  • Endotoxins
  • Flavanones
  • Lipopolysaccharides
  • Nitric Oxide Synthase Type II
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • wogonin