Differential Effects of Components in Artemisia annua Extract on the Induction of Drug-Metabolizing Enzyme Expression Mediated by Nuclear Receptors.
Differential Effects of Components in Artemisia annua Extract on the Induction of Drug-Metabolizing Enzyme Expression Mediated by Nuclear Receptors.
复制标题
青蒿提取物中的成分对核受体介导的药物代谢酶表达诱导的不同作用。
DOI：
10.1055/a-1178-0852
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发表时间：
2020
期刊：
影响因子：
2.7
通讯作者：
Xing Jie
中科院分区：
文献类型：
--
作者：
Zhang Xueli;Meng Ran;Wang Haina;Xing Jie
在一些发展中国家，青蒿是用于治疗和预防疟疾的常用剂型。但反复饮用可导致疗效明显下降，这可能与青蒿素对代谢酶的诱导作用有关。本研究采用双荧光素酶报告基因系统，研究了一年生猕猴桃中不同成分对甾烷X受体和组成型雄烷受体的激活能力。采用实时荧光定量PCR和Western blotting检测细胞色素P450 3A 4和2B 6 mRNA和蛋白表达的变化。结果表明，在CYP 3A 4报告基因系统中，金精素和青蒿素B对CYP 3A 4受体wt的诱导作用较弱，青蒿素A对CYP 3A 4受体wt和CYP 3A 4受体370的诱导作用较强，对CYP 3A 4受体163的诱导作用较弱。在胆甾烷X受体介导的CYP 2B 6中 在报告基因系统中，青蒿素A对β-内酰胺酶X受体wt和β-内酰胺酶X受体379有中等诱导作用，对β-内酰胺酶X受体403有弱诱导作用，而青蒿素B对β-内酰胺酶X受体wt和β-内酰胺酶X受体379有弱诱导作用。青蒿素A对组成型雄甾烷受体介导的CYP 3A 4/2B 6报告基因系统中的组成型雄甾烷受体3有较强的诱导作用，而青蒿素B对组成型雄甾烷受体介导的CYP 2B 6报告基因系统中的组成型雄甾烷受体3有较弱的诱导作用。CYP 3A 4和CYP 2B 6的mRNA和蛋白质表达在雄甾烷X受体或组成型雄甾烷受体被激活时增加。存在于黄花蒿中的各种成分差异地影响了异黄酮X受体亚型和组成型雄烷受体的活性，这表明了药物相互作用的可能性。这部分 解释了重复饮用一年生芦荟后药效的下降。
Artemisia annuatea 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 inA. annuato 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 inA. annuadifferentially 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 ofA. annuatea.