Grape seed proanthocyanidin extract (GSPE) successfully diminished pulmonary fibrosis induced by bleomycin (BLM) in mice, suggesting a possible therapeutic use in patients with idiopathic pulmonary fibrosis (IPF), as published in Oxidative Medicine and Cellular Longevity.

The experimental study conducted by Sul et al compared cellular and molecular characteristics observed in mice with BLM-induced pulmonary fibrosis treated with GSPE vs a control group treated with phosphate-buffered saline. Histological changes and collagen deposits decreased in the group that received GSPE, with a reduction of epithelial apoptosis through blocking oxidative stress.

Further in vitro analysis showed this effect in cellular apoptosis could be associated with the downregulation of the B-cell lymphoma protein 2-associated X/B-cell lymphoma protein 2 expressions and reduction in the ratio. Moreover, the total number of cells decreased in the bronchoalveolar lavage, and a reduction of interleukin-6 expression suggests an effect against lung inflammation and early fibrosis, while reduction of transforming growth factor β1 may be responsible for the decreased late fibrosis seen in mice treated with GSPE.

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Finally, the higher levels of hydrogen peroxide previously evidenced due to BLM successfully decreased after GSPE administration; this finding was consistent in both mice and in vitro experiments.

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Studies show that IPF still lacks definite treatment options, and although steroids, pyridones, and kinase inhibitors are currently used, their effectiveness is limited with high rates of adverse effects; hence there remains a search for therapeutic options. The authors hypothesized GSPE as a treatment for IPF due to its known antioxidant capacity, useful against the oxidative stress that creates alveolar injury, inflammation, and subsequent fibrosis in this disease.

“Double staining for cytokeratin and cleaved [poly adenosine diphosphate-ribose polymerase-1] showed that in the phosphate-buffered saline-treated control group, epithelial apoptosis was not found but increased in the BLM+vehicle group on day 7 after BLM instillation,” the authors said. “However, the cleaved PARP-1 expression increased after BLM administration and was significantly decreased by GSPE.”


Sul O, Kim J, Lee T, et al. GSPE protects against bleomycin-induced pulmonary fibrosis in mice via ameliorating epithelial apoptosis through inhibition of oxidative stress. Oxid Med Cell Longev. Published online March 20, 2022. doi:10.1155/2022/8200189