Eucalyptus Compound Found to Reduce Lung Damage in PF Sheep

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by Steve Bryson, PhD |

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Pinocembrin, a compound isolated from eucalyptus trees, significantly reduced the signs and symptoms of lung damage in a sheep model of pulmonary fibrosis (PF), a study demonstrated.

“We found that pinocembrin improved lung function, attenuated [eased the effect of] lung inflammation, and decreased overall pathology scores compared to damaged lungs that were untreated,” Habamu Derseh, PhD, of the Melbourne Veterinary School at the University of Melbourne, in Australia, and co-lead author of the study, said in a university press release.

Derseh described the compound’s effects as “striking.” Researchers noted that sheep are “a large animal model for human lung disease.”

The study, “The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis,” was published in the journal PLOS One.

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Pinocembrin is a flavonoid, or a type of plant pigment, found in several kinds of trees, including pines and eucalyptus. Studies suggest it has anti-inflammatory, antioxidant, anti-microbial, and anti-cancer properties.

Importantly, studies have shown that pinocembrin can halt the process of scarring, or fibrosis — the development of fibrous connective tissue as a repair response to tissue injury or damage — in several different animal models of disease.

Progressive scarring and inflammation of lung tissue are underlying disease processes of PF. Although current treatments slow the progression of the disease, they are unable to stop it.

Given the properties of pinocembrin, Derseh, in collaboration with researchers from Monash University and Swinburne University of Technology, both also in Melbourne, and industry partner Gretals Australia, a technology company, evaluated the impact of pinocembrin isolated from eucalyptus trees on a sheep model of induced PF.

“In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis,” the team wrote.

Researchers induced lung fibrosis in two lung segments of 10 sheep with the chemical bleomycin. Fibrosis developed in small, isolated regions of the lungs (5-10%) which allowed otherwise normal lung function.

The team isolated and purified pinocembrin from the leaves of three-year-old eucalyptus trees. Then, once weekly for four weeks, 7 mg of pinocembrin were infused into a single lung segment in each sheep, while the other segment was left untreated.

The animals continued to gain weight as expected, had normal white blood cell counts, and showed no adverse effects during the treatment period.

As expected, segments of the lung that received bleomycin alone had a significantly lower mean function — meaning more difficult to inflate and stiffer lung tissue — compared with healthy control lung segments.

With pinocembrin administration, bleomycin-treated lung segments had better function, which was not significantly different from healthy lung segments. Further, pinocembrin-treated lung segments significantly improved over the four-week (about one month) treatment period.

Immune cells were then counted in bronchoalveolar lavage (BAL) fluid, collected after rinsing the lungs in a small volume of saline solution.

While healthy control lung samples had relatively low numbers of inflammatory cells in the BAL fluid, samples exposed to bleomycin had significantly higher numbers of immune cells called neutrophils as well as other inflammatory cells. Treatment with pinocembrin significantly lowered the number of neutrophils and certain inflammatory cells in lung segments exposed to bleomycin.

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“In lung fluid samples, inflammatory cells called neutrophils dropped from 7.4 percent of total cells to 3.7 percent in the pinocembrin-treated bleomycin-injured lung segments,” said Ken Snibson, PhD, a study co-author, who noted the change represented a 50% reduction in neutrophils.

In addition, there were relatively low numbers of immune T-cells in healthy lung parenchyma — the portion of the lung involved in the transfer of oxygen and carbon dioxide. After exposure to bleomycin, the T-cell counts significantly increased, whereas, in fibrotic lung segments that received pinocembrin, the T-cell counts significantly decreased.

Markers for inflammation, fibrosis, and overall disease were then assessed in lung tissue samples. As expected, normal healthy lung tissue had low scores for each parameter assessed, while lung tissue segments injured by bleomycin had significantly high mean scores for each marker tested.

Treatment with pinocembrin significantly reduced inflammatory and overall disease scores in lung segments exposed to bleomycin. Pinocembrin infusion also lowered fibrosis scores compared with untreated tissue, but the difference was not statistically significant.

“We saw striking anti-inflammatory effects and modest anti-fibrotic remodeling after four weeks of administering pinocembrin,” Derseh said.

Microscopic analysis showed that pinocembrin treatment reduced the amount of connective tissue induced by bleomycin. Tissue samples collected from all 10 animals showed bleomycin exposure significantly increased the levels of the protein collagen, a major component of connective tissue. Pinocembrin treatment, however, did not reduce the increase in collagen.

“In conclusion, the strong and significant data derived from this study [were] consistent with pinocembrin being bioactive and improving key disease parameters in the animal model setting,” the researchers wrote. “The striking anti-inflammatory and modest anti-fibrotic remodelling effects of pinocembrin administration were likely linked to its ability to improve lung pathology and [lung function].”

Given these positive results, the team has plans to launch clinical trials to test the compound in humans.

“This started with an ARC Linkage Grant between Gretals Australia and Professor Ian Woodrow (School of Ecosystem and Forest Sciences) and Dr Goodger to identify and isolate pinocembrin from native eucalyptus trees, and now we have progressed to the stage where we are preparing for human trials in 2022,” said Alistair Cumming, Gretals Australia CEO and study co-author.