Pan M H, Huang T M, Lin J K
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Drug Metab Dispos. 1999 Apr;27(4):486-94.
Curcumin, the yellow pigment in turmeric and curry, has antioxidative and anticarcinogenic activities. In this study, we investigated the pharmacokinetic properties of curcumin in mice. After i.p. administration of curcumin (0.1 g/kg) to mice, about 2.25 microg/ml of curcumin appeared in the plasma in the first 15 min. One hour after administration, the levels of curcumin in the intestines, spleen, liver, and kidneys were 177.04, 26.06, 26.90, and 7.51 microg/g, respectively. Only traces (0.41 microg/g) were observed in the brain at 1 h. To clarify the nature of the metabolites of curcumin, the plasma was analyzed by reversed-phase HPLC, and two putative conjugates were observed. Treatment of the plasma with beta-glucuronidase resulted in a decrease in the concentrations of these two putative conjugates and the concomitant appearance of tetrahydrocurcumin (THC) and curcumin, respectively. To investigate the nature of these glucuronide conjugates in vivo, the plasma was analyzed by electrospray. The chemical structures of these metabolites, determined by mass spectrometry/mass spectrometry analysis, suggested that curcumin was first biotransformed to dihydrocurcumin and THC and that these compounds subsequently were converted to monoglucuronide conjugates. Because THC is one of the major metabolites of curcumin, we studied its stability at different pH values. THC was very stable in 0.1 M phosphate buffers of various pH values. Moreover, THC was more stable than curcumin in 0.1 M phosphate buffer, pH 7.2 (37 degrees C). These results, together with previous findings, suggest that curcumin-glucuronoside, dihydrocurcumin-glucuronoside, THC-glucuronoside, and THC are major metabolites of curcumin in vivo.
姜黄素是姜黄和咖喱中的黄色色素，具有抗氧化和抗癌活性。在本研究中，我们研究了姜黄素在小鼠体内的药代动力学特性。给小鼠腹腔注射姜黄素（0.1 g/kg）后，最初15分钟血浆中出现约2.25微克/毫升的姜黄素。给药1小时后，姜黄素在肠道、脾脏、肝脏和肾脏中的含量分别为177.04、26.06、26.90和7.51微克/克。1小时时在大脑中仅观察到微量（0.41微克/克）。为了阐明姜黄素代谢物的性质，采用反相高效液相色谱法分析血浆，观察到两种假定的共轭物。用β-葡萄糖醛酸酶处理血浆导致这两种假定共轭物的浓度降低，并分别同时出现四氢姜黄素（THC）和姜黄素。为了研究体内这些葡萄糖醛酸共轭物的性质，采用电喷雾法分析血浆。通过质谱/质谱分析确定的这些代谢物的化学结构表明，姜黄素首先生物转化为二氢姜黄素和THC，随后这些化合物转化为单葡萄糖醛酸共轭物。由于THC是姜黄素的主要代谢物之一，我们研究了其在不同pH值下的稳定性。THC在各种pH值的0.1 M磷酸盐缓冲液中非常稳定。此外，在pH 7.2（37℃）的0.1 M磷酸盐缓冲液中，THC比姜黄素更稳定。这些结果与先前的发现一起表明，姜黄素-葡萄糖苷、二氢姜黄素-葡萄糖苷、THC-葡萄糖苷和THC是姜黄素在体内的主要代谢物。
