Phenolic and flavonoid content and in vitro inhibitory effect of some Amazonian fruit juices on CYP3A4 activity

ABSTRACT Many foods interact with drugs and may cause changes in the pharmacological effects of the co-administered therapeutic agent. The enzyme CYP3A4, which belongs to the cytochrome P450 enzyme complex, is responsible for the metabolism of most drugs currently on the market and is involved in many drug interactions. Hence, the interaction of this enzyme with juices of some fruits, such as grapefruit, can affect the pharmacokinetics of various drugs. However, native fruits from the Amazon region have not yet been the target of this type of research. We determined total polyphenols and flavonoids of the Amazonian fruits açaí (Euterpe precatoria), buriti (Mauritia flexuosa), camu-camu (Myrciaria dubia), cubiu (Solanum sessiliflorum), cupuaçu (Theobroma grandiflorum), jenipapo (Genipa americana), and taperebá (Spondias mombin) and evaluated the effects of each fruit juice on CYP3A4 activity, using the star fruit (Averrhoa carambola) juice as positive control. Açaí juice presented the highest content of total polyphenols and flavonoids (102.6 ± 7.2 µg gallic acid equivalent (GAE) per mL and 7.2 ± 0.6 µg quercetin equivalent (QE) per mL, respectively). All juices were able to inhibit the activity of CYP3A4. There was no residual activity of the drug-metabolizing enzyme for açai, buriti, cubiu, camu-camu, and taperebá juice, while for cupuaçu, jenipapo and the positive control, the residual activity was 44.3, 54.3 and 20.2%, respectively. Additional studies should identify the phytocompound(s) responsible for this inhibition activity, to clarify the mechanisms involved in this phenomenon.

摘要：许多食物可与药物发生相互作用，进而改变联合给药治疗剂的药理效应。细胞色素P450酶复合物（cytochrome P450 enzyme complex）中的CYP3A4酶，负责代谢目前市场上绝大多数药物，并参与众多药物相互作用过程。因此，该酶与西柚等部分果汁的相互作用，可影响多种药物的药代动力学特征。然而，亚马逊本土水果尚未成为此类研究的关注对象。本研究测定了亚马逊地区七种本土水果的总多酚与总黄酮含量，分别为巴西莓（Euterpe precatoria）、布里蒂果（Mauritia flexuosa）、卡姆果（Myrciaria dubia）、库比乌果（Solanum sessiliflorum）、古布阿苏果（Theobroma grandiflorum）、杰尼帕果（Genipa americana）以及塔佩雷巴果（Spondias mombin）；并以杨桃（Averrhoa carambola）果汁作为阳性对照，评估各水果果汁对CYP3A4酶活性的影响。其中巴西莓果汁的总多酚与总黄酮含量最高，分别为每毫升102.6±7.2 μg没食子酸当量（gallic acid equivalent, GAE）与7.2±0.6 μg槲皮素当量（quercetin equivalent, QE）。所有受试果汁均能抑制CYP3A4酶活性。巴西莓、布里蒂果、库比乌果、卡姆果以及塔佩雷巴果汁处理组的药物代谢酶无残留活性；而古布阿苏果、杰尼帕果处理组与阳性对照组的酶残留活性分别为44.3%、54.3%与20.2%。后续研究需明确介导该抑制活性的植物成分，以阐明此类相互作用的潜在机制。