Effects of polyphenols extracted from Keemun black tea on CYP450s activity and molecular mechanisms

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.