School of Pharmaceutical Sciences, Shandong University, Jinan, R. P. China.
Planta Med. 2020 Aug;86(12):867-875. doi: 10.1055/a-1178-0852. Epub 2020 Jun 17.
tea is a popular dosage form used to treat and prevent malaria in some developing countries. However, repeated drinking leads to an obviously decreased efficacy, which may be related to the induction of metabolizing enzymes by artemisinin. In the present study, the ability of different components in to activate the pregnane X receptor and constitutive androstane receptor was evaluated by the dual luciferase reporter gene system. The changes in mRNA and protein expression of CYP3A4 and CYP2B6 were determined by quantitative real-time PCR and Western blotting. Results showed that in the pregnane X receptor-mediated CYP3A4 reporter gene system, chrysosplenetin and arteannuin B exhibited a weak induction effect on pregnane X receptor wt, while arteannuin A had a strong induction effect on pregnane X receptor wt and pregnane X receptor 370 and a weak induction effect on pregnane X receptor 163. In the pregnane X receptor-mediated CYP2B6 reporter gene system, arteannuin A had a moderate induction effect on pregnane X receptor wt and pregnane X receptor 379, and a weak induction effect on pregnane X receptor 403, while arteannuin B had a weak induction effect on pregnane X receptor wt and pregnane X receptor 379. Arteannuin A had a strong induction effect on constitutive androstane receptor 3 in constitutive androstane receptor-mediated CYP3A4/2B6 reporter gene systems, while arteannuin B showed a weak induction effect on constitutive androstane receptor 3 in the constitutive androstane receptor-mediated CYP2B6 reporter gene system. The mRNA and protein expressions of CYP3A4 and CYP2B6 were increased when the pregnane X receptor or constitutive androstane receptor was activated. Various components present in differentially affect the activities of pregnane X receptor isoforms and the constitutive androstane receptor, which indicates the possibility of a drug-drug interaction. This partly explains the decline in efficacy after repeated drinking of tea.
茶是一种在一些发展中国家用于治疗和预防疟疾的流行剂型。然而，重复饮用会导致疗效明显下降，这可能与青蒿素诱导代谢酶有关。本研究采用双荧光素酶报告基因系统评价了 中不同成分激活孕烷 X 受体和组成型雄烷受体的能力。采用实时定量 PCR 和 Western blot 法测定 CYP3A4 和 CYP2B6 的 mRNA 和蛋白表达变化。结果表明，在孕烷 X 受体介导的 CYP3A4 报告基因系统中，当曲酸和青蒿素 B 对野生型孕烷 X 受体有较弱的诱导作用时，青蒿素 A 对野生型孕烷 X 受体和孕烷 X 受体 370 有较强的诱导作用，对孕烷 X 受体 163 有较弱的诱导作用。在孕烷 X 受体介导的 CYP2B6 报告基因系统中，青蒿素 A 对野生型孕烷 X 受体和孕烷 X 受体 379 有中等强度的诱导作用，对孕烷 X 受体 403 有较弱的诱导作用，而青蒿素 B 对野生型孕烷 X 受体和孕烷 X 受体 379 有较弱的诱导作用。青蒿素 A 对组成型雄烷受体 3 在组成型雄烷受体介导的 CYP3A4/2B6 报告基因系统中具有较强的诱导作用，而青蒿素 B 对组成型雄烷受体 3 在组成型雄烷受体介导的 CYP2B6 报告基因系统中表现出较弱的诱导作用。当激活孕烷 X 受体或组成型雄烷受体时，CYP3A4 和 CYP2B6 的 mRNA 和蛋白表达增加。 中存在的各种成分不同程度地影响孕烷 X 受体同工酶和组成型雄烷受体的活性，提示可能存在药物相互作用。这部分解释了重复饮用 茶后疗效下降的原因。
