A flavanone from Baccharis retusa (Asteraceae) prevents elastase-induced emphysema in mice by regulating NF-κB, oxidative stress and metalloproteinases

Abstract

BackgroundPulmonary emphysema is characterized by irreversible airflow obstruction, inflammation, oxidative stress imbalance and lung remodeling, resulting in reduced lung function and a lower quality of life. Flavonoids are plant compounds with potential anti-inflammatory and antioxidant effects that have been used in folk medicine. Our aim was to determine whether treatment with sakuranetin, a flavonoid extracted from the aerial parts of Baccharis retusa, interferes with the development of lung emphysema.MethodsIntranasal saline or elastase was administered to mice; the animals were then treated with sakuranetin or vehicle 2 h later and again on days 7, 14 and 28. We evaluated lung function and the inflammatory profile in bronchoalveolar lavage fluid (BALF). The lungs were removed to evaluate alveolar enlargement, extracellular matrix fibers and the expression of MMP-9, MMP-12, TIMP-1, 8-iso-PGF-2α and p65-NF-κB in the fixed tissues as well as to evaluate cytokine levels and p65-NF-κB protein expression.ResultsIn the elastase-treated animals, sakuranetin treatment reduced the alveolar enlargement, collagen and elastic fiber deposition and the number of MMP-9- and MMP-12-positive cells but increased TIMP-1 expression. In addition, sakuranetin treatment decreased the inflammation and the levels of TNF-α, IL-1β and M-CSF in the BALF as well as the levels of NF-κB and 8-iso-PGF-2α in the lungs of the elastase-treated animals. However, this treatment did not affect the changes in lung function.ConclusionThese data emphasize the importance of oxidative stress and metalloproteinase imbalance in the development of emphysema and suggest that sakuranetin is a potent candidate that should be further investigated as an emphysema treatment. This compound may be useful for counteracting lung remodeling and oxidative stress and thus attenuating the development of emphysema.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0233-3) contains supplementary material, which is available to authorized users.

A Review on Sources and Pharmacological Aspects of Sakuranetin

“…In the sakuranetin-treated emphysematous animals, reductions in lung inflammation, which were associated with attenuated lung parenchymal remodeling and in alveolar destruction, were observed. Sakuranetin treatment reduced lung inflammation and pro-inflammatory cytokine levels (M-CSF, TNF-α, IL-1β, MCP-1 and MIP-2) in lung homogenates [77].…”

Therapeutic Potential of Medicinal Plants and Their Constituents on Lung Inflammatory Disorders

“…Under this condition, sakuranetin reduced the NF-κB response (Taguchi et al ., 2015). It also regulated the expression of MMPs.…”

The in vivo hepato-recovery effects of the polyphenol-rich fermented food Xeniji™ on ethanol-induced liver damage

“…In addition, both 5-O-caffeoylquinic acid and 3-O-caffeoylquinic acid were also reported to have an in vitro liver protective effect against carbon tetrachloride (CCl 4 ) challenges. 20 Sakuranetin is a avonoid that has been previously reported to have antioxidant 21 and anti-inammatory effects, [21][22][23] which may contribute to the in vitro antiinammatory effect of Xeniji. 9 The presence of these polyphenols contributed to the antioxidant effect of Xeniji 10 and provided evidence that Xeniji may possess a hepato-recovery effect.…”

“…Previous studies have reported that sakuranetin possesses anti-inammatory effects by inhibiting the NF-kB pathway. 21 The anti-inammatory effect of the phenolic acids of Xeniji helps to prevent the formation of reactive peroxynitrite and TNF-a, which induce apoptosis of hepatic cells.…”