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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.

Derochette S, Mouithys-Mickalad A, Franck T, Collienne S, Ceusters J, Deby-Dupont G, Neven P, Serteyn D - FEBS Open Bio (2014)

Bottom Line: 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.Our results, showed that NDS27 is the best inhibitor for Nox2 and PKCδ.

View Article: PubMed Central - PubMed

Affiliation: Center for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée du 6 Août 13, B-4000 Liège, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of NDS27 (A), HPβCD (B), NDS28 (C) or γ-CD (D) concentration (black lines) on the residual activities of PKCδ (%). A horizontal light gray line shows the inflection points of the curves corresponding to the IC50.
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f0010: Effect of NDS27 (A), HPβCD (B), NDS28 (C) or γ-CD (D) concentration (black lines) on the residual activities of PKCδ (%). A horizontal light gray line shows the inflection points of the curves corresponding to the IC50.

Mentions: The hill slopes characteristic of the curve shapes were calculated for each condition and a hill slope higher than −0.4 would mean that the curve was not sigmoidal, very flat or not descending. As observed in Fig. 2A and C, the shape of the dose–response curves with NDS27 and NDS28 were sigmoidal as confirmed by the hill slopes lower than −0.4 (−1.37 and −1.23 respectively). The IC50 determined for the two molecules were quite similar: 1.67 × 10−5 M for NDS27 and 1.26 × 10−5 M for NDS28. For HPβCD and γ-CD the hill slopes were higher than −0.4 showing no inhibition (Fig. 2B and D).


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.

Derochette S, Mouithys-Mickalad A, Franck T, Collienne S, Ceusters J, Deby-Dupont G, Neven P, Serteyn D - FEBS Open Bio (2014)

Effect of NDS27 (A), HPβCD (B), NDS28 (C) or γ-CD (D) concentration (black lines) on the residual activities of PKCδ (%). A horizontal light gray line shows the inflection points of the curves corresponding to the IC50.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4254746&req=5

f0010: Effect of NDS27 (A), HPβCD (B), NDS28 (C) or γ-CD (D) concentration (black lines) on the residual activities of PKCδ (%). A horizontal light gray line shows the inflection points of the curves corresponding to the IC50.
Mentions: The hill slopes characteristic of the curve shapes were calculated for each condition and a hill slope higher than −0.4 would mean that the curve was not sigmoidal, very flat or not descending. As observed in Fig. 2A and C, the shape of the dose–response curves with NDS27 and NDS28 were sigmoidal as confirmed by the hill slopes lower than −0.4 (−1.37 and −1.23 respectively). The IC50 determined for the two molecules were quite similar: 1.67 × 10−5 M for NDS27 and 1.26 × 10−5 M for NDS28. For HPβCD and γ-CD the hill slopes were higher than −0.4 showing no inhibition (Fig. 2B and D).

Bottom Line: 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.Our results, showed that NDS27 is the best inhibitor for Nox2 and PKCδ.

View Article: PubMed Central - PubMed

Affiliation: Center for Oxygen, R&D (CORD), Institute of Chemistry, B6a, University of Liège, Allée du 6 Août 13, B-4000 Liège, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus