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目的:在抑郁症动物模型上分析姜黄素药代动力学、药效动力学及其效应特征。方法:在强迫游泳 (FST)小鼠上分别单次和重复灌胃给予 2.5, 5 和 10 mg?kg-1姜黄素。分别测定脑区单胺氧化酶 A(MAO-A)活性及动物行为。采用 HPLC方法测定血浆中姜黄素水平。利用兼有滞后时间的二房室模型分析姜黄素药代动力学。结果:口服给予姜黄素,血药浓度峰值分别出现给药 0.75 h (单次)和 2.75-3 h (重复)后,其检测限大约在 6 h (单次)和 14 h (重复)内。毫微克级姜黄素血药浓度状态下,可呈现出 FST 小鼠 MAO-A 的抑制活性及行为的改善作用。姜黄素对 FST 小鼠攀爬、游泳、不动等异常行为的逆转作用分别在口服给药 1-2 h (单次)和 3-4 h (重复) 后达到最大效应,这与其抑制前额叶皮层和海马 MAO-A 活性的时效一致。结论:这些研究结果表明姜黄素可能不直接产生改善抑郁行为作用,其效应也可能不依赖于其血药浓度。
OBJECTIVE: To analyze the pharmacokinetics, pharmacodynamics and effects of curcumin on animal models of depression. Methods: Single, repeated and intragastric administration of 2.5, 5 and 10 mg? Kg-1 curcumin in forced swimming (FST) mice respectively. The activity of monoamine oxidase A (MAO-A) and the animal behavior were measured respectively. Plasma levels of curcumin were determined by HPLC method. Analysis of curcumin pharmacokinetics using two compartment model with lag time. RESULTS: Curcumin was orally administered with the detection limits of about 6 h (single) and 14 h (repeat) after peak drug concentrations of 0.75 h (single) and 2.75 to 3 h (repeat), respectively. Under the condition of the concentration of curcumin of nanogram level, the inhibitory activity of MAO-A in FST mice and the improvement of the behavior can be shown. The reversal effects of curcumin on climbing, swimming and immobility in FST mice were maximal after 1-2 h (single) and 3-4 h (repetitive) administration, respectively, which was not related to its inhibition of prefrontal cortex Aging of MAO-A activity in the cortex and hippocampus is time-consistent. CONCLUSIONS: These findings suggest that curcumin may not directly contribute to the improvement of depression behavior and its effect may or may not be dependent on its plasma concentration.