Clinical significance
• Eperisone may be safer and more therapeutically beneficial
for IPF patients
than current therapies.
ABSTRACT
Background and purpose: Although the exact pathogenesis of
idiopathic pulmonary fibrosis (IPF) is still unknown, the
transdifferentiation of fibroblasts into myofibroblasts and the
production of extracellular matrix components such as collagen,
triggered by alveolar epithelial cell injury, are important mechanisms
of IPF development. In the lungs of IPF patients, apoptosis is less
likely to be induced in fibroblasts than in alveolar epithelial cells,
and this process is involved in the pathogenesis of IPF.
Experimental approach: We used a library containing approved
drugs to screen for drugs that preferentially reduce cell viability in
LL29 cells (lung fibroblasts from an IPF patient) compared with A549
cells (human alveolar epithelial cell line).
Key results: After screening, we selected eperisone, a central
muscle relaxant used in clinical practice. Eperisone showed little
toxicity in A549 cells and preferentially reduced the percentage of
viable LL29 cells, while pirfenidone and nintedanib did not have this
effect. Eperisone also significantly inhibited transforming growth
factor-β1-dependent transdifferentiation of LL29 cells into
myofibroblasts. In an in vivo study using ICR mice, eperisone
inhibited bleomycin (BLM)-induced pulmonary fibrosis, respiratory
dysfunction, and fibroblast activation. In contrast, pirfenidone and
nintedanib were less effective than eperisone in inhibiting BLM-induced
pulmonary fibrosis under this experimental condition. Finally, we showed
that eperisone did not induce adverse effects in the liver and
gastrointestinal tract in the BLM-induced pulmonary fibrosis model.
Conclusion and implications: Considering these results, we
propose that eperisone may be safer and more therapeutically beneficial
for IPF patients than current therapies.