Zuo Dan, Lv Le, Ren Hong, Sun Haiyan
School of Food and Drug Shenzhen Polytechnic University Shenzhen Guangdong China.
Vocational and Technical College of Anshun Anshun Guizhou China.
Food Sci Nutr. 2024 Jul 19;12(10):7306-7315. doi: 10.1002/fsn3.4319. eCollection 2024 Oct.
Keemun black tea (KBT) is a luxurious traditional tea in China that has been commonly consumed because of its superior aroma and special taste. However, the risks remain unknown when KBT is used concomitantly with other drugs or food products. Therefore, we aimed to explore the effect of the tea polyphenols from KBT on the protein and mRNA levels of CYP450 and related mechanisms. The extraction of tea polyphenols from KBT and the content and component analysis of polyphenols were performed. A total of 24 female C57BL/6J mice were given tea polyphenols (0, 75, 150, 300 mg/kg) for 7 days, respectively. Liver tissues were collected 2 h after the last administration. The expression of Cyp3a11, Cyp1a2, Cyp2e1, Cyp2c37, and PXR mRNA was detected by real-time PCR, and the expression of Cyp3a11, Cyp1a2, Cyp2e1, Cyp2c37, and PXR protein was detected by Western blotting. A transient co-transfection reporter gene assay on HepG2 cells was also used to verify the role of PXR in regulating CYP3A4 expression. Our results showed that tea polyphenols from KBT significantly induced the expression of CYP 3A11 and PXR in general, inhibited the expression of Cyp1a2 and Cyp2e1 in general, and significantly inhibited the mRNA expression of Cyp2c37 but induced its protein expression. The reporter gene-transfected cells demonstrated that tea polyphenols could enhance the PXR-mediated transactivation of the CYP3A4 promoter via rifampicin-induction. Meanwhile, tea polyphenols could significantly accelerate CYP3A11/3A4 expression by activating the PXR-CYP3A4 pathway. In conclusion, KBT polyphenols could significantly affect the expression of various subtypes of the Cyp450 enzyme in mice livers via the PXR-CYP450 pathway, suggesting that metabolism-based interactions can occur when they are used in combination with medicines.
祁门红茶（KBT）是中国一种名贵的传统茶叶，因其香气浓郁、口感独特而备受青睐。然而，祁门红茶与其他药物或食品同时使用时的风险尚不清楚。因此，我们旨在探讨祁门红茶中的茶多酚对细胞色素P450（CYP450）蛋白和mRNA水平的影响及其相关机制。我们进行了祁门红茶中茶多酚的提取以及茶多酚的含量和成分分析。将24只雌性C57BL/6J小鼠分别给予茶多酚（0、75、150、300mg/kg），持续7天。末次给药2小时后收集肝脏组织。通过实时聚合酶链反应（PCR）检测Cyp3a11、Cyp1a2、Cyp2e1、Cyp2c37和孕烷X受体（PXR）mRNA的表达，通过蛋白质免疫印迹法检测Cyp3a11、Cyp1a2、Cyp2e1、Cyp2c37和PXR蛋白的表达。还采用在人肝癌细胞系（HepG2）细胞上进行瞬时共转染报告基因分析，以验证PXR在调节细胞色素P450 3A4（CYP3A4）表达中的作用。我们的研究结果表明，祁门红茶中的茶多酚总体上显著诱导CYP 3A11和PXR的表达，总体上抑制Cyp1a2和Cyp2e1的表达，显著抑制Cyp2c37的mRNA表达，但诱导其蛋白表达。报告基因转染细胞显示，茶多酚可通过利福平诱导增强PXR介导的CYP3A4启动子的反式激活。同时，茶多酚可通过激活PXR-CYP3A4途径显著加速CYP3A11/3A4的表达。总之，祁门红茶多酚可通过PXR-CYP450途径显著影响小鼠肝脏中Cyp450酶各亚型的表达，提示其与药物联合使用时可能发生基于代谢的相互作用。
