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?

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 (O 2 − ), superoxide dismutase (SOD), hydrogen peroxide (H 2 O 2 ) 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 O 2 − -release. Results 1,8-cineole (10 −5  M) strongly inhibited O 2 − (−53%, p  2 O 2 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  Conclusions We report an inhibition of superoxide anions, balancing partial dismutation of superoxide anions and independent inhibition of H 2 O 2 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.