Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
J Ethnopharmacol. 2013 Sep 16;149(2):543-9. doi: 10.1016/j.jep.2013.07.014. Epub 2013 Jul 20.
Traditional Chinese Medicine (TCM) has become more popular among cancer patients in the Western world, who often use Chinese herbs as adjuvant therapy to reduce the adverse effects of conventional chemotherapy. However, pharmacokinetic (PK) interactions between Chinese herbs and anticancer drugs can occur and have dramatic consequences for these patients. Currently, only a few possible PK interactions between Chinese herbs and conventional Western drugs have been documented.
Since the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) contributes to most of the PK interactions with (anticancer) drugs, the effect of four Chinese herbs (Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus) on the activity and expression of CYP3A4 was investigated in vitro.
Ethanol and water-ethanol extracts of the four Chinese herbs were prepared from raw material. CYP3A4 inhibition was assessed by the use of Supersomes™ in a fluorescence assay. Furthermore, CYP3A4 induction was evaluated in a human pregnane X receptor (hPXR)-mediated CYP3A4 reporter gene assay and a quantitative real time PCR assay, both in human colon adenocarcinoma-derived LS180 cells (LS180).
Extracts of Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus inhibited CYP3A4 in human CYP3A4 Supersomes™ (IC50 values: 17-83 µg/mL). Oldenlandia diffusa and Rehmannia glutinosa significantly induced PXR-mediated CYP3A4 (p<0.001). Oldenlandia diffusa also significantly induced CYP3A4 mRNA levels (p<0.001 at 250 µg/mL).
Concomitant use of Oldenlandia diffusa and Rehmannia glutinosa could result in induction of CYP3A4, leading to a reduced efficacy of drugs that are CYP3A4 substrates and have a narrow therapeutic window. Because of the possible enhanced toxicity caused by CYP3A4 inhibition, clinical effects of CYP3A4 inhibition by Astragalus propinquus and Codonopsis tangshen must also be taken into account. In conclusion, herb-drug interactions between Chinese herbs and various CYP3A4 substrates can occur. Further research to investigate the clinical relevance of the interactions caused by Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus is required.
来自中国和德国的研究团队发现，四种常见中草药可能会改变癌症治疗药物的疗效。
草药在西方世界的癌症患者中越来越受欢迎，他们经常将中药作为辅助疗法，以减少常规化疗的副作用。然而，中药与抗癌药物之间可能会发生药代动力学（PK）相互作用，这对这些患者有重大影响。目前，只有少数文献记录了中药与传统西药之间可能存在的 PK 相互作用。
由于细胞色素 P450 3A4（CYP3A4）酶参与了大多数与（抗癌）药物的 PK 相互作用，因此本研究在体外研究了四种中药（白花蛇舌草、党参、地黄和黄芪）对 CYP3A4 活性和表达的影响。
从原材料中制备了四种中药的乙醇和水-乙醇提取物。使用 Supersomes™在荧光测定中评估 CYP3A4 抑制作用。此外，在人结肠癌衍生的 LS180 细胞（LS180）中，通过人孕烷 X 受体（hPXR）介导的 CYP3A4 报告基因测定和定量实时 PCR 测定评估 CYP3A4 诱导。
白花蛇舌草、党参、地黄和黄芪提取物在人 CYP3A4 Supersomes™中抑制 CYP3A4（IC50 值：17-83 µg/mL）。白花蛇舌草和地黄显着诱导 PXR 介导的 CYP3A4（p<0.001）。白花蛇舌草还显着诱导 CYP3A4 mRNA 水平（250 µg/mL 时 p<0.001）。
同时使用白花蛇舌草和地黄可能导致 CYP3A4 诱导，从而降低 CYP3A4 底物的药物疗效，并导致治疗窗狭窄。由于 CYP3A4 抑制可能导致增强的毒性，因此还必须考虑黄芪和党参的 CYP3A4 抑制的临床效果。总之，中药与各种 CYP3A4 底物之间可能发生草药-药物相互作用。需要进一步研究来调查白花蛇舌草、党参、地黄和黄芪引起的相互作用的临床相关性。
