Wogonin Attenuates Bleomycin-Induced Pulmonary Fibrosis and Oxidative Stress Injury via the MAPK Signaling Pathway

Biol Pharm Bull. 2024;47(12):2165-2172. doi: 10.1248/bpb.b24-00534.

Abstract

Idiopathic pulmonary fibrosis (PF) is an irreversible and chronic inflammatory condition with limited therapeutic options and a high mortality rate. We aimed to determine the possible role and mechanisms of wogonin (WGN) on PF. A rat model of PF was established with intratracheally administrated with bleomycin (BLM), followed by intravenously injecting with WGN and weekly body weight measurements for four weeks. Hematoxylin-eosin (H&E) and Masson's trichrome staining were implemented for histopathological analysis. In addition, the levels of fibrotic proteins and indicators of the mitogen-activated protein kinase (MAPK) pathway were assessed with Western blot. RT-quantitative (q)PCR experiment was conducted to investigate the fibrotic proteins' mRNA expression. Ultimately, the concentrations of glutathione peroxidase (GSH-PX), malonaldehyde (MDA), and superoxide dismutase (SOD) were ascertained with appropriate kits. The results showed that WGN administration significantly reversed BLM-induced body weight reduction, alleviated pathological fibrosis, and reduced the Ashcroft score and the lung wet-to-dry weight ratio. Additionally, WGN suppressed the rise of fibrotic protein levels in BLM-treated rat's lung tissues. Furthermore, WGN attenuated BLM-stimulated oxidative stress, as evidenced by the increased GSH-PX and SOD levels and decreased MDA levels in vivo. Finally, wogonin supplements significantly lowered the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK phosphorylation levels in the BLM-treated rat's lung tissues. In conclusion, our study proved that PF induced by BLM administration can be mitigated by WGN treatment via suppressing the MAPK pathway, indicating that WGN is a candidate therapeutic agent for managing PF.

Keywords: idiopathic pulmonary fibrosis; mitogen-activated protein kinase (MAPK); oxidative stress; wogonin.

MeSH terms

  • Animals
  • Bleomycin* / toxicity
  • Flavanones* / pharmacology
  • Flavanones* / therapeutic use
  • Glutathione Peroxidase / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • MAP Kinase Signaling System* / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress* / drug effects
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / metabolism
  • Pulmonary Fibrosis* / pathology
  • Rats
  • Rats, Sprague-Dawley*
  • Superoxide Dismutase / metabolism

Substances

  • Bleomycin
  • Flavanones
  • wogonin
  • Superoxide Dismutase
  • Glutathione Peroxidase
  • Malondialdehyde