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

Taguchi L, Pinheiro NM, Olivo CR, Choqueta-Toledo A, Grecco SS, Lopes FD, Caperuto LC, Martins MA, Tiberio IF, Câmara NO, Lago JH, Prado CM - Respir. Res. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, Universidade Federal de São Paulo, Rua Artur Riedel, 275 - Eldorado, Diadema, SP, Brazil.

ABSTRACT

Background: 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. 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.

Methods: Intranasal 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.

Results: In 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.

Conclusion: These 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.

No MeSH data available.


Related in: MedlinePlus

NF-κB in lung tissue. NF-κB-positive area (mean and SE) in the lung parenchyma a. Representative photomicrographs of the lung parenchyma immunostained for NF-κB b-d. Vehicle-treated animals that received elastase showed an increase in the NF-κB-positive area c compared with animals in the control group b. This response was attenuated in elastase animals by sakuranetin treatment d; compared with the ELA+Ve group c. NF-kB protein content and a representative Western blot of NF-kB e-f. The Western blot corroborates the immunohistochemistry data. *p < 0.05 compared with the SAL+Ve group; **p < 0.05 compared with the ELA+Ve group
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Fig5: NF-κB in lung tissue. NF-κB-positive area (mean and SE) in the lung parenchyma a. Representative photomicrographs of the lung parenchyma immunostained for NF-κB b-d. Vehicle-treated animals that received elastase showed an increase in the NF-κB-positive area c compared with animals in the control group b. This response was attenuated in elastase animals by sakuranetin treatment d; compared with the ELA+Ve group c. NF-kB protein content and a representative Western blot of NF-kB e-f. The Western blot corroborates the immunohistochemistry data. *p < 0.05 compared with the SAL+Ve group; **p < 0.05 compared with the ELA+Ve group

Mentions: We quantified the NF-κB-positive cells in lung tissue (Fig. 5a-d) by immunohistochemistry and determined the NF-κB protein content in lung homogenates by Western blotting (Fig. 5e-f). NF-κB expression, as examined by immunostaining and Western blotting, was higher in the animals that received elastase (ELA+Ve) compared with those that received saline (SAL+Ve) (p < 0.05). Treating the elastase-instilled animals with sakuranetin reduced both the number of NF-κB-positive cells and the NF-κB content (ELA+SK vs ELA+Ve; p < 0.05). Treatment with sakuranetin did not affect NF-κB expression in the control groups. Photomicrographs of the lung tissue immunostained for NF-κB are shown in Fig. 5b-d. Intense positive staining was observed in the animals that received elastase (c), and this positive staining was reduced by sakuranetin treatment (d). A representative blot is shown in Fig. 5f.Fig. 5


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

Taguchi L, Pinheiro NM, Olivo CR, Choqueta-Toledo A, Grecco SS, Lopes FD, Caperuto LC, Martins MA, Tiberio IF, Câmara NO, Lago JH, Prado CM - Respir. Res. (2015)

NF-κB in lung tissue. NF-κB-positive area (mean and SE) in the lung parenchyma a. Representative photomicrographs of the lung parenchyma immunostained for NF-κB b-d. Vehicle-treated animals that received elastase showed an increase in the NF-κB-positive area c compared with animals in the control group b. This response was attenuated in elastase animals by sakuranetin treatment d; compared with the ELA+Ve group c. NF-kB protein content and a representative Western blot of NF-kB e-f. The Western blot corroborates the immunohistochemistry data. *p < 0.05 compared with the SAL+Ve group; **p < 0.05 compared with the ELA+Ve group
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4489216&req=5

Fig5: NF-κB in lung tissue. NF-κB-positive area (mean and SE) in the lung parenchyma a. Representative photomicrographs of the lung parenchyma immunostained for NF-κB b-d. Vehicle-treated animals that received elastase showed an increase in the NF-κB-positive area c compared with animals in the control group b. This response was attenuated in elastase animals by sakuranetin treatment d; compared with the ELA+Ve group c. NF-kB protein content and a representative Western blot of NF-kB e-f. The Western blot corroborates the immunohistochemistry data. *p < 0.05 compared with the SAL+Ve group; **p < 0.05 compared with the ELA+Ve group
Mentions: We quantified the NF-κB-positive cells in lung tissue (Fig. 5a-d) by immunohistochemistry and determined the NF-κB protein content in lung homogenates by Western blotting (Fig. 5e-f). NF-κB expression, as examined by immunostaining and Western blotting, was higher in the animals that received elastase (ELA+Ve) compared with those that received saline (SAL+Ve) (p < 0.05). Treating the elastase-instilled animals with sakuranetin reduced both the number of NF-κB-positive cells and the NF-κB content (ELA+SK vs ELA+Ve; p < 0.05). Treatment with sakuranetin did not affect NF-κB expression in the control groups. Photomicrographs of the lung tissue immunostained for NF-κB are shown in Fig. 5b-d. Intense positive staining was observed in the animals that received elastase (c), and this positive staining was reduced by sakuranetin treatment (d). A representative blot is shown in Fig. 5f.Fig. 5

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, Universidade Federal de São Paulo, Rua Artur Riedel, 275 - Eldorado, Diadema, SP, Brazil.

ABSTRACT

Background: 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. 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.

Methods: Intranasal 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.

Results: In 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.

Conclusion: These 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.

No MeSH data available.


Related in: MedlinePlus