The soluble curcumin derivative NDS27 inhibits superoxide anion production by neutrophils and acts as substrate and reversible inhibitor of myeloperoxidase

Abstract

A water-soluble curcumin lysinate incorporated into hydroxypropyl-β-cyclodextrin (NDS27) has been developed and shown anti-inflammatory properties but no comparative study has been made in parallel with its parent molecule, curcumin on polymorphonuclear neutrophils (PMNs) and myeloperoxidase (MPO) involved in inflammation. The effect of NDS27, its excipients (hydroxypropyl-β-cyclodextrin and lysine), curcumin lysinate and curcumin were compared on the release of superoxide anion by PMNs using a chemiluminescence assay and on the enzymatic activity of MPO. It was shown that curcumin and NDS27 exhibit similar inhibition activities on superoxide anion release by stimulated PMNs but also on MPO peroxidase and halogenation activities. The action mechanism of curcumin and NDS27 on the MPO activity was refined by stopped-flow and docking analyses. We demonstrate that both curcumin and NDS27 are reversible inhibitors of MPO by acting as excellent electron donors for redox intermediate Compound I (∼10 7 M −1 s −1) but not for Compound II (∼10 3 M −1 s −1) in the peroxidase cycle of the enzyme, thereby trapping the enzyme in the Compound II state. Docking calculations show that curcumin is able to enter the enzymatic pocket of MPO and bind to the heme cavity by πstacking and formation of hydrogen bonds involving substituents from both aromatic rings. Hydroxypropyl-βcyclodextrin is too bulky to enter MPO channel leading to the binding site suggesting a full release of curcumin from the cyclodextrin thereby allowing its full access to the active site of MPO. In conclusion, the hydroxypropylβ-cyclodextrin of NDS27 enhances curcumin solubilization without affecting its antioxidant capacity and inhibitory activity on MPO.

Antitoxic Effects of Curcumin against Obesity-Induced Multi-Organs’ Biochemical and Histopathological Abnormalities in an Animal Model

“…These results were in agreement with those achieved by Fu et al [ 50 ], who found that curcumin attenuated the infiltration of inflammatory cells and the activity of MPO. Also, our results are in line with Franck et al [ 65 ], who demonstrated that curcumin is a reversible inhibitor of MPO by acting as an excellent electron donor in the peroxidase cycle of the enzyme.…”

Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase

“…Dilutions of the cell suspension and reagents were performed to work with a final volume of 200 µL. The superoxide anion production was measured by chemiluminescence (CL) according to Franck et al [ 25 ], but L-012 was used as a chemiluminescent probe. L-012 is a luminol analogue generally used to measure reactive oxygen and nitrogen species (RNOS) in inflammatory situations, especially superoxide anions derived from NADPH oxidase activity [ 26 ]; it is also used to detect HOCl formation resulting from MPO activity [ 27 ].…”

“…The SIEFED assay was used as a pharmacological tool for the screening of MPO inhibitors [ 25 ]. One million mdMSCs were suspended in 1 mL HBSS and serial dilutions were performed to obtain cell suspensions ranging from 100,000 to 195 cells in 500 µL HBSS.…”

Neurobehavioral protective properties of curcumin against the mercury chloride treated mice offspring

“…Curcumin also contains neuroprotective effects and are useful to treat neurodegenerative disorders (Cole et al, 2007, Abu-Taweel GM, 2016). Many studies have revealed that curcumin exhibits various antioxidant properties (Ciftci et al, 2012, Kunihiro et al, 2019, Tao et al, 2019, Franck et al, 2019, Chaudhary et al, 2019, Mukherjee et al, 2019, Wu et al, 2019). In general, commercially available curcumin contains approximately 3% bisdemethoxycurcumin, 17% de- methoxycurcumin and 77% curcumin (Abu-Taweel et al, 2013).…”