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.
Highlights
Pulmonary 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
Chemical characterization of sakuranetin The isolated flavonoid was characterized based on analysis by nuclear magnetic resonance (NMR) (1H and 13C) and lowresolution electronic impact mass spectrometry (LREIMS)
In the present study, we evaluated whether sakuranetin derived from the plant Baccharis retusa interferes with the inflammatory changes and destruction of lung tissue that is observed in an experimental murine emphysema model generated by the intranasal instillation of elastase
Summary
Pulmonary 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. The main feature of chronic obstructive pulmonary disease (COPD) is pulmonary airflow restriction that is not fully reversible; this limitation is usually progressive and is associated with an abnormal inflammatory response to the inhalation of noxious particles and gases. Three states of COPD have been well described; these states can occur concomitantly or separately and include narrowed airway thickness, limited expiratory airflow, and increased production of secretions, which induces chronic cough and emphysema. Emphysema, which develops in 15 % to 20 % of smokers and 1 % of non-smokers [2], is defined as an airspace enlargement that is usually induced by oxidative stress and an imbalance between proteases and antiproteases that leads to inflammatory processes. The transcription factor nuclear factor-kappa B (NF-κB) controls the expression of many of the inflammatory and apoptotic genes present in COPD [4]
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