Biotransformation of curcumin through reduction and glucuronidation in mice.
Biotransformation of curcumin through reduction and glucuronidation in mice.
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发表时间：
1999-04
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通讯作者：
M. Pan;Tsang-Miao Huang;Jen-kun Lin
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作者：
M. Pan;Tsang-Miao Huang;Jen-kun Lin
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。在这项研究中，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，在前15分钟内血浆中出现约2.25 μ g/ml的姜黄素。给药后1小时，肠、脾、肝和肾中的姜黄素水平分别为177.04、26.06、26.90和7.51 μ g/g。在1小时时，仅在脑中观察到痕量（0.41微克/克）。为了阐明姜黄素代谢产物的性质，通过反相HPLC分析血浆，并观察到两种推定的缀合物。用β-葡萄糖醛酸苷酶处理血浆导致这两种推定缀合物的浓度降低，并分别伴随出现四氢姜黄素（THC）和姜黄素。为了研究这些葡糖苷酸结合物在体内的性质，通过电喷雾分析血浆。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，这些化合物随后转化为单葡糖苷酸缀合物。由于THC是姜黄素的主要代谢产物之一，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，THC在0.1M磷酸盐缓冲液，pH 7.2（37 ℃）中比姜黄素更稳定。这些结果，连同以前的研究结果，表明姜黄素-葡萄糖醛酸苷，二氢姜黄素-葡萄糖醛酸苷，THC-葡萄糖醛酸苷，和THC是姜黄素在体内的主要代谢产物。
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.