title: NDS27 combines the effect of curcumin lysinate and hydroxypropyl-β-cyclodextrin to inhibit equine PKCδ and NADPH oxidase involved in the oxidative burst of neutrophils.
abstract: Polymorphonuclear neutrophils (PMNs) are involved in host defence against infections by the production of reactive oxygen species (ROS), but excessive PMN stimulation is associated with the development of inflammatory diseases. After appropriate stimuli, protein kinase C (PKC) triggers the assembly of NADPH oxidase (Nox2) which produces superoxide anion (O2 (•) (-)), from which ROS derive. The therapeutic use of polyphenols is proposed to lower ROS production by limiting Nox2 and PKC activities. The purpose of this study was to compare the antioxidant effect of NDS27 and NDS28, two water-soluble forms of curcumin lysinate respectively complexed with hydroxypropyl-β-cyclodextrin (HPβCD) and γ-cyclodextrin (γ-CD), on the activity of Nox2 and PKCδ, involved in the Nox2 activation pathway. Our results, showed that NDS27 is the best inhibitor for Nox2 and PKCδ. This was illustrated by the combined effect of HPβCD and curcumin lysinate: HPβCD, but not γ-CD, improved the release of curcumin lysinate and its exchange against lipid or cholesterol as demonstrated by the lipid colouration with Oil Red O, the extraction of radical lipophilic probes recorded by ESR and the HPLC measurements of curcumin. HPβCD not only solubilised and transported curcumin, but also indirectly enhanced its action on both PKC and Nox2 activities. The modulatory effect of NDS27 on the Nox2 activation pathway of neutrophils may open therapeutic perspectives for the control of pathologies with excessive inflammatory reactions.
authors.affiliation: Center for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée du 6 Août 13, B-4000 Liège, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Derochette
authors.affiliation: Center for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée du 6 Août 13, B-4000 Liège, Belgium.
authors.forename: Ange
authors.initials: A
authors.lastname: Mouithys-Mickalad
authors.affiliation: Center for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée du 6 Août 13, B-4000 Liège, Belgium ; Faculty of Veterinary Medicine, Equine Clinic, B41, University of Liège, Boulevard de Colonster 20, B-4000 Liège, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Franck
authors.affiliation: Department of Physics, Biomedical Spectroscopy, B5a, University of Liège, Allée du 6 Août 17, B-4000 Liège, Belgium.
authors.forename: Simon
authors.initials: S
authors.lastname: Collienne
authors.affiliation: Center for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée du 6 Août 13, B-4000 Liège, Belgium.
authors.forename: Justine
authors.initials: J
authors.lastname: Ceusters
authors.affiliation: Center for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée du 6 Août 13, B-4000 Liège, Belgium.
authors.forename: Ginette
authors.initials: G
authors.lastname: Deby-Dupont
authors.affiliation: Faculty of Pharmacy, Laboratory of Medicinal Chemistry, B36, University of Liège, Avenue de l'Hôpital, 1, B-4000 Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Neven
authors.affiliation: Center for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée du 6 Août 13, B-4000 Liège, Belgium ; Faculty of Veterinary Medicine, Equine Clinic, B41, University of Liège, Boulevard de Colonster 20, B-4000 Liège, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Serteyn
keywords: Curcumin lysinate; Cyclodextrin; HPβCD, hydroxypropyl-β-cyclodextrin; Inflammation; MPO, myeloperoxidase; NADPH oxidase; PKC; PMNs, polymorphonuclear neutrophils; ROS, reactive oxygen species; fMLP, formyl-methionyl-leucyl-phenylalanine; γ-CD, γ-cyclodextrin