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 (∼10⁷ M⁻¹ s⁻¹) but not for Compound II (∼10³ 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 π-stacking and formation of hydrogen bonds involving substituents from both aromatic rings. Hydroxypropyl-β-cyclodextrin 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 hydroxypropyl-β-cyclodextrin of NDS27 enhances curcumin solubilization without affecting its antioxidant capacity and inhibitory activity on MPO.

已开发出一种可溶于羟丙基-β-环糊精（NDS27）的水溶性姜黄素赖氨酸盐，具有抗炎特性，但尚未与其母体分子姜黄素对多形核中性粒细胞（PMN）和髓过氧化物酶（MPO）进行平行研究）参与炎症。使用化学发光分析比较了NDS27，其赋形剂（羟丙基-β-环糊精和赖氨酸），姜黄素赖氨酸盐和姜黄素对PMNs释放超氧阴离子和MPO酶活性的影响。结果表明姜黄素和NDS27对受刺激的PMN释放超氧阴离子具有相似的抑制活性，但对MPO过氧化物酶和卤化活性也具有类似的抑制活性。姜黄素和NDS27对MPO活性的作用机理通过停流和对接分析得以完善。⁷  M ^-1  s ^-1），但不适用于化合物II（〜10 ³  M ^-1  s ^-1）在酶的过氧化物酶循环中，从而将酶捕获为化合物II状态。对接计算表明，姜黄素能够通过π堆积和涉及两个芳香环上的取代基的氢键形成而进入MPO的酶口袋并与血红素腔结合。羟丙基-β-环糊精太大，无法进入MPO通道，导致结合位点，表明姜黄素从环糊精中完全释放出来，从而使其能够完全进入MPO的活性位点。总之，NDS27的羟丙基-β-环糊精可增强姜黄素的增溶作用，而不会影响其抗氧化能力和对MPO的抑制活性。