Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
Ann Pharmacother. 2010 Jun;44(6):1038-45. doi: 10.1345/aph.1M533. Epub 2010 May 18.
Curcumin is a kind of plant polyphenol that is extracted from the rhizome of Curcuma longa. Studies about the effect of curcumin on the activity of drug-metabolizing enzymes in humans are lacking.
To investigate the effect of curcumin on the activities of CYP1A2, CYP2A6, N-acetyltransferase (NAT2), and xanthine oxidase (XO) in vivo, using caffeine as a probe drug.
Sixteen unrelated, healthy Chinese men were recruited for the study. There were 2 phases in the study. In the first phase, volunteers orally received 100 mg caffeine and 0- to 12-hour blood and urine samples were collected. In the second phase, volunteers received 1000 mg curcumin once daily for 14 continuous days, and blood and urine samples were collected on day 15, following the same procedure used on the first day. Urinary caffeine metabolite ratios were used as the indicators of the activities of CYP1A2, CYP2A6, NAT2, and XO. The pharmacokinetics of caffeine and its metabolites were determined by high-performance liquid chromatography.
In the curcumin-treated group, CYP1A2 activity was decreased by 28.6% (95% CI 15.6 to 41.8; p < 0.000), while increases were observed in CYP2A6 (by 48.9%; 95% CI 25.3 to 72.4; p < 0.000). Plasma area under the curve from zero to 12 hours of 1,7-dimethylxanthine (17X) was decreased by 27.2% (95% CI 6.1 to 48.3; p = 0.014). The urinary excretion of 17X and 1-methylxanthine was significantly decreased by 36.4% (95% CI 19.4 to 53.6; p < 0.000) and 31.2% (95% CI 8.5 to 54.1; p = 0.010), respectively. The excretion of 1,7-dimethylurate (17U) was significantly increased by 77.3% (95% CI 5.6 to 148.8; p = 0.036). No significant changes were observed for caffeine, 1-methylurate, and 5-acetylamino-6-formylamino-3-methyluracil between the 2 study phases.
The results indicated that curcumin inhibits CYP1A2 function but enhances CYP2A6 activity. Simultaneously, some pharmacokinetic parameters relating to 17X were affected by curcumin. If this finding is confirmed by other studies, the possibility of herb-drug interactions associated with curcumin should be considered in clinical practice.
姜黄素是一种从姜黄根茎中提取的植物多酚。关于姜黄素对人体药物代谢酶活性的影响的研究还很缺乏。
以咖啡因作为探针药物，研究姜黄素对 CYP1A2、CYP2A6、N-乙酰基转移酶（NAT2）和黄嘌呤氧化酶（XO）活性的体内影响。
招募了 16 名无关的健康中国男性志愿者参与本研究。研究分为 2 个阶段。在第一阶段，志愿者口服 100mg 咖啡因，并采集 0 至 12 小时的血样和尿样。在第二阶段，志愿者连续 14 天每天口服 1000mg 姜黄素，在第 15 天按照第一天的相同程序采集血样和尿样。尿咖啡因代谢物比值用作 CYP1A2、CYP2A6、NAT2 和 XO 活性的指标。咖啡因及其代谢物的药代动力学通过高效液相色谱法确定。
在姜黄素治疗组中，CYP1A2 活性下降 28.6%（95%CI 15.6 至 41.8；p<0.000），而 CYP2A6 活性增加 48.9%（95%CI 25.3 至 72.4；p<0.000）。1，7-二甲基黄嘌呤（17X）的血浆 AUC0-12 小时减少了 27.2%（95%CI 6.1 至 48.3；p=0.014）。17X 和 1-甲基黄嘌呤的尿排泄量分别显著减少了 36.4%（95%CI 19.4 至 53.6；p<0.000）和 31.2%（95%CI 8.5 至 54.1；p=0.010）。1，7-二甲基尿酸（17U）的排泄量显著增加了 77.3%（95%CI 5.6 至 148.8；p=0.036）。在两个研究阶段之间，咖啡因、1-甲基尿酸和 5-乙酰氨基-6-甲酰氨基-3-甲基尿嘧啶的药代动力学参数没有明显变化。
结果表明，姜黄素抑制 CYP1A2 功能，但增强 CYP2A6 活性。同时，17X 的一些药代动力学参数受到姜黄素的影响。如果这一发现得到其他研究的证实，在临床实践中应考虑与姜黄素相关的草药-药物相互作用的可能性。
