Intra- and extracellular antioxidant capacities of the new water-soluble form of curcumin (NDS27) on stimulated neutrophils and HL-60 cells

in Chemico-Biological Interactions (2013), 201(1-3), 49-57

Phagocytic cells, especially neutrophils (PMNs) are specialized in the production of reactive oxygen species (ROS) to kill pathogenic agents, but an excessive ROS production is associated with tissue ... [more ▼]

Phagocytic cells, especially neutrophils (PMNs) are specialized in the production of reactive oxygen species (ROS) to kill pathogenic agents, but an excessive ROS production is associated with tissue damages and inflammatory diseases. Phagocytes are thus prime therapeutic targets to control inflammatory events associated to ROS production. Nowadays, there is a growing interest for the use of polyphenols to modulate the inflammatory response. The aim of this work was to study the antioxidant effect of NDS27, a highly water-soluble form of the polyphenolic molecule curcumin, on in vitro stimulated equine PMNs and human promyelocytic leukemia cells (HL-60). NDS27 was either pre-incubated with cells and eliminated before their activation (intracellular effect) or let in the medium (extracellular effect). Our results indicate that NDS27 significantly and dose-dependently (10 6 M–10 4 M) inhibited the ROS production in both cell types without affecting their viability. NDS27 was able to cross and interact with cell membrane, especially for HL-60 cells, while we observed a better intracellular antioxidant effect with PMNs. The activity of myeloperoxidase (MPO) released by PMNs and HL-60 cells, was decreased by NDS27, but more efficiently for PMNs. These results suggested that the greater efficiency of NDS27 in PMNs is due to an inhibitory effect on cells which are more mature for ROS production, probably by targeting the enzymes implied in respiratory burst like MPO. The modulatory effect of NDS27 on the oxidant activity of cells involved in immune and inflammatory responses opens perspectives for a therapeutic control of pathologies with excessive inflammatory reactions. [less ▲]

Possible intracellular effect of the new water-soluble form of curcumin (NDS27) on the oxidant response of stimulated neutrophils

Poster (2012, April 18)

Neutrophils (PMNs) are involved in host defense against infections through the production of reactive oxygen species (ROS) to kill pathologic agents. But, an excessive ROS production, called “oxidative ... [more ▼]

Neutrophils (PMNs) are involved in host defense against infections through the production of reactive oxygen species (ROS) to kill pathologic agents. But, an excessive ROS production, called “oxidative stress” is associated with tissue damages and development of chronic or acute inflammatory diseases. PMNs are prime therapeutic targets to control inflammatory events associated to ROS production. Nowadays, there is a growing interest for the use of polyphenolic molecules to modulate the inflammatory response. The aim of this work was to study the antioxidant effect of NDS27 (1), a new highly water-soluble form of the polyphenolic molecule curcumin, on in vitro stimulated equine PMNs. NDS27 (10-6 to 10-4 M) was pre-incubated with cells and eliminated before their activation. The ability of NDS27 to enter into the cells was checked by HPLC from the cellular extracts. The intracellular ROS production by phorbol myristate acetate (PMA) stimulated PMNs was measured by fluorescence using 2’,7’-dichlorofluorescin diacetate. Lucigenin dependent chemiluminescence was used to measure extracellular ROS production. Additionally, the effect of NDS27 was tested on the activity of myeloperoxidase (MPO), a hemic enzyme contributing to the oxidant response of neutrophils. The activity of the released MPO by cytochalazine B (CB) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) stimulated PMNs was measured by SIEFED (“Specific Immunologic Extraction Followed by Enzymatic Detection”) (2). The HPLC results showed that NDS27 enters into PMNs and interacts with their membrane. NDS27 significantly and dose-dependently inhibited the ROS production in neutrophils without affecting their viability. Likewise, the activity of MPO released by PMNs was lowered by NDS27. Overall, our findings demonstrate that the membrane of neutrophils is permeable to NDS27 or interacts with the drug, suggesting that its inhibitory effect on ROS production is mainly associated to an intracellular effect probably by acting on the enzymes implied in respiratory burst like NADPH oxidase and MPO. The modulatory effect of NDS27 towards the oxidant activity of cells involved in immune and inflammatory response open therapeutic perspectives to control equine or human pathologies with excessive inflammatory reactions. 1. Neven et al. 2011, Patent Application Publication: US2011/0257126 A1 2. Serteyn et al. 2005, European Patent Specification : EP1711817 B1 [less ▲]

WATER SOLUBLE CURCUMIN COMPOSITIONS FOR USE IN ANTI-CANCER AND ANTI-INFLAMMATORY THERAPY

Patent (2011)

The present invention relates to the medical field. In a first aspect the present invention relates to novel water soluble cyclodextrin-curcumin complexes having a pharmacological activity, in particular ... [more ▼]

The present invention relates to the medical field. In a first aspect the present invention relates to novel water soluble cyclodextrin-curcumin complexes having a pharmacological activity, in particular an anti-tumour and/or anti-inflammatory activity, and improved physico-chemical properties. In a second aspect, the present invention relates to a method for preparation of said water soluble curcumin derivatives. The invention further relates in a third aspect to a pharmaceutical composition comprising an effective amount of said water soluble curcumin derivatives. In a fourth aspect, the present invention concerns the use of said water soluble cucumin derivatives as a medicament and the use of said water soluble curcumin derivatives for the preparation of a medicament for the treatment of cancer and inflammatory diseases. In a fifth aspect, the present invention relates to the use of a pharmaceutical composition comprising said water soluble curcumin derivatives in the treatment of cancer and inflammatory diseases and to a new pharmaceutical composition comprising said water soluble curcumin derivatives. [less ▲]

Inhalation with NDS27 attenuates pulmonary neutrophilic inflammation in recurrent airway obstruction

in Veterinary Record : Journal of the British Veterinary Association (2011)

AMADEOX method : combination of various techniques to distinguish stoichiometric and anticatalytic activities of antioxidant molecules or natural extracts

in International Society of Antioxidants in Nutrition & Health, 5th International Conference on Polyphenols Applications, Bridging Bioefficacy to Innovations & Applications, October 29th-30th 2009, Malta (2009, October 29)

We developed an original method called AMADEOX (for « Action Modulatrice de l'Activité Des Enzymes Oxydantes ») able to distinguish stoichiometric, metabolic and anticatalytic activities of antioxidant ... [more ▼]

We developed an original method called AMADEOX (for « Action Modulatrice de l'Activité Des Enzymes Oxydantes ») able to distinguish stoichiometric, metabolic and anticatalytic activities of antioxidant molecules or natural extracts on stimulated neutrophils and purified myeloperoxidase (MPO), a key enzyme released by neutrophil and acting as one of the major ROS generating systems. [less ▲]

Inhibitory Effect of Curcuminoids and Tetrahydrocurcuminoids on Equine Activated Neutrophils and Myeloperoxidase Activity

in Physiological Research (2007), 57(4), 577-587

In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen ... [more ▼]

In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcuminoids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO. The ROS production and the release of MPO by activated neutrophils were measured by chemiluminescence and ELISA techniques, respectively. The activity of purified MPO was measured by studying its nitration, chlorination or oxidation capacity and by using an original method called SIEFED allowing the study of drug interaction with the enzyme without interferences of the medium. Curcuminoids and THC had dose-dependent inhibitory effects on ROS production and MPO release by activated neutrophils and on purified MPO activity. We suggest that the higher efficacy of curcuminoids versus THC could be explained, at least partially, by its chemical structure: the conjugated double bounds and the plane structure of curcuminoids made easier the neutralization of the radical species generated by activated neutrophils and the interaction of the drug with the active site of MPO. These inhibitory effects of curcuminoids on the oxidant activity of equine neutrophils and on MPO activity open therapeutic perspectives in equine pathologies with excessive inflammatory reactions. [less ▲]

Synthesis and biological evaluation of new 3-aralkylamino-2-aryl-2H-1,2,4-pyridothiadiazine 1,1-dioxides as potential CCK receptor ligands

in Journal of Pharmacy & Pharmacology (1997), 49

WATER-SOLUBLE NIMESULIDE SALT, AND USES THEREOF FOR THE TREATMENT OF INFLAMMATIONS

Patent (1995)

Water-soluble nimesulide salt comprised of the product obtained from the reaction of nimesulide and L-lysine, preparation thereof, aqueous solution containing it, associations based on nimesulide with ... [more ▼]

Water-soluble nimesulide salt comprised of the product obtained from the reaction of nimesulide and L-lysine, preparation thereof, aqueous solution containing it, associations based on nimesulide with cyclodextrins, and uses thereof. [less ▲]