姜黄素和莪术二酮在大鼠和人肝微粒体中的代谢动力学特征：CYP 酶的参与。
Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes.
机构信息
School of Pharmaceutical Sciences, Guangxi Medical University, Nanning 530021, China.
Guangxi-ASEAN Food Inspection and Testing Center, Nanning 530029, China.
出版信息
Molecules. 2022 Jul 14;27(14):4482. doi: 10.3390/molecules27144482.
Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC-MS/MS (ultrahigh-pressure liquid chromatography-tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The V of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the V of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication-drug and drug-enzyme interactions.
姜黄素和姜烯酮是姜科植物中的天然产物，具有多种生物学特性。其中，抗非小细胞肺癌（NSCLC）的作用值得关注。本文采用超高效液相色谱-串联质谱法（UP-HPLC-MS/MS），在大鼠肝微粒体（RLMs）、人肝微粒体（HLMs）和细胞色素 P450（CYP）酶（CYP3A4、1A2、2E1 和 2C19）的 NADPH 生成体系中，对这两种化合物的动力学进行了评估。通过 Western blot 法在体外和体内检测了两种化合物对四种细胞色素 P450（CYP）酶含量的影响。姜黄素在 RLMs 中的 t 为 22.35 min，在 HLMs 中的 t 为 173.28 min，而姜烯酮的 t 分别为 18.02 和 16.37 min。RLMs 中姜黄素的 V 约为 HLMs 中的 4 倍，同时，RLMs 中姜烯酮的 V 与 HLMs 相似。姜黄素在 CYP3A4 中的单酶 t1/2 为 38.51 min，在 1A2 中的 t1/2 为 301.4 min，在 2E1 中的 t1/2 为 69.31 min，在 2C19 中的 t1/2 为 63.01 min；而对于相同的酶，姜烯酮的 t1/2 分别为 36.48 min、86.64 min、69.31 min 和 57.76 min。通过合理的实验设计获得了动力学曲线，并选择 RLMs/HLMs 中姜黄素和姜烯酮的代谢。在两种肝微粒体中，化合物的降解性能存在选择性差异。这些结果意味着在临床用药-药物和药物-酶相互作用中，应更加关注药物。
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