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Dose-dependent bioavailability indicators for curcumin and two of its novel derivatives

机译：姜黄素及其两种新型衍生物的剂量依赖性生物利用度指标

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Novel water-soluble curcumin derivatives have been developed to overcome low in vivo bioavailability of curcumin. The aim of this work is to assess the potential utility of certain downstream targets as bioavailability indicators of systemic activity of pure curcumin and two novel water-soluble curcumin derivatives (NCD) by constructing dose-dependent response curves and to prove whether this novel curcumin derivatives retained, improved, or abolished biological activity of pure curcumin when applied in vivo. Pure curcumin (CUR), curcumin-carboxy derivative (NCD-1), and curcumin protein conjugate (NCD-2) were administered orally to rats at escalating doses: 37, 74, 148, and 296 lM/kg body weight, respectively. Plasma levels of GST activity, cavernous tissue levels of cGMP, and enzymatic activity of both HO-1 and GST were assessed one and half and 24 hours after oral administration of curcumin formulae. This study showed that there was a progressive elevation of cavernous tissue levels of cGMP and enzymatic activity of both HO-1 and GST in a dose-dependent manner that was maintained for 24 h with CUR, NCD-1, and NCD-2. Plasma GST activity was decreased by the lowest doses on the curve. The three dose-dependent bioavailability indicators as surrogates of curcumin and two of its novel derivatives are valid in the studied range of concentration and extended time. The novel curcumin derivatives still conserve with improvement the biological activity of natural curcumin when applied in vivo.
机译：已经开发了新型水溶性姜黄素衍生物以克服姜黄素的体内生物利用度低。这项工作的目的是通过构建剂量依赖性反应曲线来评估某些下游目标作为纯姜黄素和两种新型水溶性姜黄素衍生物（NCD）全身活性的生物利用度指标的潜在效用，并证明这种新型姜黄素衍生物是否当在体内应用时，保留，改善或消除了姜黄素的生物学活性。将纯姜黄素（CUR），姜黄素羧基衍生物（NCD-1）和姜黄素蛋白偶联物（NCD-2）分别以递增剂量：37、74、148和296 lM / kg体重口服给予大鼠。在口服姜黄素配方后半小时和24小时评估血浆GST活性，cGMP海绵组织水平以及HO-1和GST的酶活性。这项研究表明，海绵状组织中cGMP的水平逐渐升高，HO-1和GST的酶活性呈剂量依赖性，并在CUR，NCD-1和NCD-2的作用下维持24小时。血浆GST活性降低了曲线上的最低剂量。作为姜黄素的替代物的三种剂量依赖性生物利用度指标及其两种新衍生物在所研究的浓度和延长时间范围内有效。当在体内应用时，新型姜黄素衍生物仍保留改善天然姜黄素的生物学活性。

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