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Sodium cromoglycate exerts anti-pulmonary fibrosis effects by targeting the Keap1 protein to activate Nrf2 signaling

  • 0Department of Pharmacology, School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang 110016, China.
Bioorganic Chemistry +

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November 18, 2024

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November 18, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Sodium cromoglycate (Cro) directly binds Keap1, activating the Nrf2 pathway to combat oxidative stress. This compound shows promise in treating pulmonary fibrosis by reducing inflammation and fibrosis in cellular and animal models.

Area Of Science

  • Biochemistry
  • Pharmacology
  • Cell Biology

Background

  • Pulmonary fibrosis (PF) is linked to oxidative stress.
  • The Keap1-Nrf2 pathway regulates cellular redox balance.
  • Activating Nrf2 by targeting Keap1 is a potential PF treatment strategy.

Purpose Of The Study

  • To identify compounds that bind Keap1 using virtual screening.
  • To evaluate the anti-pulmonary fibrosis effects of sodium cromoglycate (Cro).

Main Methods

  • Pharmacophore-based virtual screening of FDA-approved compounds.
  • Cellular thermal shift assay (CETSA) to confirm Keap1 binding.
  • In vitro studies using TGF-β1-induced A549 cells.
  • In vivo studies using bleomycin-induced pulmonary fibrosis mouse model.

Main Results

  • Sodium cromoglycate (Cro) demonstrated high binding affinity to Keap1.
  • Cro activated Nrf2 signaling, reduced oxidative stress, and inhibited epithelial-mesenchymal transition (EMT) in vitro.
  • Cro improved lung fibrosis, activated Nrf2, and blocked EMT in vivo.

Conclusions

  • Cro directly binds Keap1, activating the Nrf2 pathway to clear reactive oxygen species (ROS).
  • Cro alleviates pulmonary fibrosis by inhibiting EMT progression both in vitro and in vivo.
  • Cro represents a potential therapeutic agent for pulmonary fibrosis.

Keywords:

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