CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal; CNC - Centre for Neuroscience and Cell Biology, 3004-504, Coimbra, Portugal.
Life Sci. 2016 Jan 1;144:30-6. doi: 10.1016/j.lfs.2015.11.004. Epub 2015 Nov 21.
Hypericum perforatum (H. perforatum) is one of the most used medicinal plants. However, it has been associated with relevant interactions with several drugs. This situation is probably mediated by cytochrome P450 enzymes (CYP450), namely the 1A2 (CYP1A2) and 2D6 (CYP2D6) isoforms This study aims to assess the cytotoxic and CYP1A2 and CYP2D6 inductive and/or inhibitory effects of a H. perforatum extract and its main bioactive components in hepatic cell lines.
A MTT proliferation assay was performed in WRL-68, HepG2 and HepaRG cells after exposition to different concentrations of H. perforatum extract, hypericin and hyperforin for 24 and 72 h. Then, a real-time PCR analysis was accomplished after incubating the cells with these products evaluating the relative CYP1A2 and CYP2D6 expression.
These products have relevant cytotoxicity at a 10 μM concentration and it was also demonstrated for the first time that H. perforatum can lead to a significant CYP1A2 and CYP2D6 induction in all cell lines. Moreover, hypericin seems to induce CYP1A2 in HepG2 cells and to inhibit its expression in HepaRG cells while hyperforin induced CYP1A2 in HepG2 and in WRL-68 cells. Additionally, hypericin and hyperforin induce CYP2D6 in HepG2 cells but inhibits its expression in HepaRG and in WRL-68 cells.
This study not only evidenced that H. perforatum extract and two of its bioactive components can have toxic effects in hepatic cell lines but also emphasized the potential risk of the consumption of H. perforatum with CYP1A2- and CYP2D6-metabolized drugs.
贯叶金丝桃（H. perforatum）是最常用的药用植物之一。然而，它与几种药物的相关相互作用有关。这种情况可能是由细胞色素 P450 酶（CYP450）介导的，即 1A2（CYP1A2）和 2D6（CYP2D6）同工酶。本研究旨在评估贯叶金丝桃提取物及其主要生物活性成分在肝细胞系中的细胞毒性以及对 CYP1A2 和 CYP2D6 的诱导和/或抑制作用。
在 WRL-68、HepG2 和 HepaRG 细胞中，用不同浓度的贯叶金丝桃提取物、金丝桃素和金丝桃苷进行 MTT 增殖测定 24 和 72 小时。然后，用这些产物孵育细胞后进行实时 PCR 分析，评估相对 CYP1A2 和 CYP2D6 的表达。
这些产物在 10 μM 浓度下具有显著的细胞毒性，并且这也是首次证明贯叶金丝桃可以在所有细胞系中显著诱导 CYP1A2 和 CYP2D6。此外，金丝桃素似乎在 HepG2 细胞中诱导 CYP1A2，并在 HepaRG 细胞中抑制其表达，而金丝桃苷在 HepG2 和 WRL-68 细胞中诱导 CYP1A2。此外，金丝桃素和金丝桃苷在 HepG2 细胞中诱导 CYP2D6，但在 HepaRG 和 WRL-68 细胞中抑制其表达。
本研究不仅证明了贯叶金丝桃提取物及其两种生物活性成分在肝细胞系中可能具有毒性作用，还强调了贯叶金丝桃与 CYP1A2 和 CYP2D6 代谢药物同时使用的潜在风险。
