Abstract
Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Methods: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. Results: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1β, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide (p < 0.05). Conclusion: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.
Highlights
Pulmonary emphysema is a main constituent of chronic obstructive pulmonary disease (COPD), which is associated to high morbidity and mortality in worldwide but commonly preventable and Molecules 2016, 21, 1390; doi:10.3390/molecules21101390 www.mdpi.com/journal/moleculesMolecules 2016, 21, 1390 treatable
The 13 C-NMR spectra of three isolated monoterpenes from essential oil from leaves of L. sidoides showed peaks of sp2 carbons at range δ 112–154 assigned to aromatic ring (C-1 to C-6) and methyl group linked to aromatic ring at δ 15–21 (C-10)
These changes were associated to high levels of nitric oxide detected in exhaled air and increase the isoprostane expression in lung tissue
Summary
Pulmonary emphysema is a main constituent of chronic obstructive pulmonary disease (COPD), which is associated to high morbidity and mortality in worldwide but commonly preventable and Molecules 2016, 21, 1390; doi:10.3390/molecules21101390 www.mdpi.com/journal/moleculesMolecules 2016, 21, 1390 treatable. It is characterized by alveolar destruction and abnormal permanent enlargement of the alveoli which leads to severe airflow limitation [1] Inflammatory cells such as neutrophils, macrophages and lymphocytes are activated and release several pro-inflammatory mediators such as interleukin. The destruction and repair process in response to the presence of chronic inflammation and oxidative stress culminate in a remodeling process which is characterized by an increase in collagen deposition and broken of elastic fibers compromising the mechanical properties of the lung [21,22]. Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Conclusion: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice
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