Poster Presentation Lorne Infection and Immunity 2022

The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis (#132)

Habtamu B Derseh 1 2 , Jason Q D Goodger 3 , Jean-Pierre Y Scheerlinck 1 , Chrishan S Samuel 4 , Ian E. Woodrow 5 , Enzo A Palombo 6 , Rob Bischof 2 , Alistair Cumming 7 , Ken Snibson 1
  1. Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia
  2. School of Science, Psychology and Sport, Federation University Australia, Berwick , Victoria, Australia
  3. School of Biosciences, University of Melbourne, Parkville, Victoria, Australia
  4. Monash Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Victoria, Australia
  5. School of Ecosystem and Forest Sciences, University of Melbourne, Parkville, Victoria, Australia
  6. Department of Chemistry and Biotechnology, Swinburne University of Technology, Hawthorn, Victoria, Australia
  7. Gretals Australia Pty Ltd, Mornington, Victoria, Australia

Background

The primary flavonoid, pinocembrin, is thought to have a variety of medical uses which relate to its reported anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. Some studies have reported that this flavonoid has anti-fibrotic activities. In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis.

Methods

Fibrosis was induced in two localised lung segments in each of the 10 sheep participating in the study. This was achieved via two bronchoscopic infusions of bleomycin into the left and right caudal lobes at a two-week interval. A third lung segment in the same sheep was left untreated and served as a healthy control segment. The animals were kept for 5 weeks after the second bleomycin infusion. Pinocembrin, isolated from Eucalyptus leaves, was administered to one of the two bleomycin-damaged lung segments at a dose of 7 mg dissolved in 5 ml 10% DMSO solution. This dose was given once-weekly over 4 weeks, starting one week after the second bleomycin infusion.

Results

Lung compliance (as a measure of stiffness) was significantly improved after four weekly administrations of pinocembrin to bleomycin-damaged lung segments. There were significantly lower numbers of neutrophils and inflammatory cells in the bronchoalveolar lavage of bleomycin-infused lung segments that were treated with pinocembrin. Compared to bleomycin-damaged lung segments without drug treatment, pinocembrin administration was associated with significantly lower numbers of CD8+ and CD4+ T cells in the lung parenchyma. Histopathology scoring data showed that pinocembrin treatment was associated with significant improvement in inflammation and overall pathology scores. Hydroxyproline analysis showed that the administration of pinocembrin did not reduce the increased lung collagen content induced by bleomycin in this model. Analyses of Masson’s Trichrome stained lung tissue sections showed that pinocembrin treatment significantly reduced the connective tissue content in lung segments exposed to bleomycin when compared to bleomycin-infused lungs that did not receive pinocembrin.

Conclusions

The striking anti-inflammatory and modest anti-fibrotic remodeling effects of pinocembrin administration were likely linked to the compound’s ability to improve lung pathology and functional compliance in this animal model of pulmonary fibrosis.