Department of New Drug Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, and Institute of Infectious Diseases, Beijing Ditan Hospital, No. 1, Xian Nong Tan Street, Beijing 100050, China.
Eur J Pharmacol. 2010 Aug 25;640(1-3):46-54. doi: 10.1016/j.ejphar.2010.05.017.
The herbal products baicalin, baicalein, chlorogenic acid, and ginsenoside Rf have multiple pharmacological effects and are extensively used in alternative and/or complementary therapies. The present study investigated whether baicalin, baicalein, chlorogenic acid, and ginsenoside Rf induced the expression of the cytochrome P450 3A4 (CYP3A4) and multi-drug resistance 1 (MDR1) genes through the pregnane X receptor and constitutive androstane receptor pathways. Real time PCR, western blotting, and a luminescent assay were used to assess the induction of gene expression and activity of CYP3A4 and MDR1 by the test compounds. The interactions of baicalein/chlorogenic acid/ginsenoside Rf with constitutive androstane receptor and pregnane X receptor were evaluated using luciferase reporter and gel shift assays. Baicalein induced the expression of CYP3A4 and MDR1 mRNA by activating pregnane X receptor and constitutive androstane receptor. Chlorogenic acid and ginsenoside Rf showed a relatively weak effect on CYP3A4 promoter activation only in HepG2 cells cotransfected with constitutive androstane receptor and demonstrated no effects on MDR1 via either the constitutive androstane receptor or pregnane X receptor pathway. Baicalin had no effect on either CYP3A4 or MDR1 gene expression. In conclusion, baicalein has the potential to up-regulate CYP3A4 and MDR1 through the direct activation of the constitutive androstane receptor and pregnane X receptor pathways. Chlorogenic acid and ginsenoside Rf only induced constitutive androstane receptor-mediated CYP3A4 expression.
中草药成分黄芩苷、黄芩素、绿原酸和人参皂苷 Rf 具有多种药理作用，广泛应用于替代和/或补充疗法。本研究探讨了黄芩苷、黄芩素、绿原酸和人参皂苷 Rf 是否通过孕烷 X 受体和组成型雄烷受体途径诱导细胞色素 P450 3A4（CYP3A4）和多药耐药基因 1（MDR1）的表达。实时 PCR、western blot 和发光测定法用于评估测试化合物对 CYP3A4 和 MDR1 基因表达和活性的诱导作用。通过荧光素酶报告基因和凝胶阻滞实验评估黄芩素/绿原酸/人参皂苷 Rf 与组成型雄烷受体和孕烷 X 受体的相互作用。黄芩素通过激活孕烷 X 受体和组成型雄烷受体诱导 CYP3A4 和 MDR1 mRNA 的表达。绿原酸和人参皂苷 Rf 仅在共转染组成型雄烷受体的 HepG2 细胞中对 CYP3A4 启动子激活表现出较弱的作用，并且通过组成型雄烷受体或孕烷 X 受体途径对 MDR1 均无作用。黄芩苷对 CYP3A4 或 MDR1 基因表达均无影响。总之，黄芩素通过直接激活组成型雄烷受体和孕烷 X 受体途径具有上调 CYP3A4 和 MDR1 的潜力。绿原酸和人参皂苷 Rf 仅诱导组成型雄烷受体介导的 CYP3A4 表达。
