Regulation of monocyte redox balance by 1,8-cineole (eucalyptol) controls oxidative stress and pro-inflammatory responses in vitro: A new option to increase the antioxidant effects of combined respiratory therapy with budesonide and formoterol?
Lisa Joy Juergens , Izabela Tuleta , Meinolf Stoeber , Kurt Racké , Uwe R. Juergens
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引用次数: 14
Abstract
Background
Airway mucus hypersecretion is the typical feature of COPD and asthma. Hypersecretion is caused by reactive oxygen species (ROS) and links the COPD-bronchitis phenotype to frequent exacerbations. Since the monoterpene 1,8-cineole is known for its secretolytic activity, we studied the antioxidant activity of 1,8-cineole.
Methods
Using a culture model of fetal calf serum (FCS)-stimulated human monocytes, we determined the effects of 1,8-cineole, at therapeutic concentrations (10−10–10−5 M) on superoxide anions (O2−), superoxide dismutase (SOD), hydrogen peroxide (H2O2) and of LPS-stimulated 8-isoprostanes (8-IsoP) and TNF-α. The effect of formoterol (F), budesonide (BUD), BUD + F without and with 1,8-cineole were determined on O2−-release.
Results
1,8-cineole (10−5 M) strongly inhibited O2− (−53%, p < 0.001), partially inhibited SOD (−28%, p = 0.0039) and inhibited H2O2 in an undulating manner at 10−10 M (−48%, p = 0.0274), while total cellular antioxidant activity as determined by inhibition of 8-IsoP increased dose-dependently from 10−6 M (−42%, p = 0.0288) to 10−5 M (−84%, p < 0.0001) comparable to TNF-α. Only weak antioxidant and, at higher concentrations, even pro-oxidant effects were detectable for F and BUD, respectively, but no pro- or antioxidant effects of F + BUD. The antioxidant effects of 1,8-cineole were not substantially influenced during co-incubation with F + BUD.
Conclusions
We report an inhibition of superoxide anions, balancing partial dismutation of superoxide anions and independent inhibition of H2O2 by 1,8-cineole. These results suggest a non-specific combined, antioxidant and anti-inflammatory mode of action of 1,8-cineole as bifunctional drug for further clinical evaluation in mild to severe COPD and as adjunctive therapy to control disease progression.
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