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Selective suppression of cytochrome P450 gene expression by the medicinal herb, Thonningia sanguinea in rat liver

机译：药草桑地黄对大鼠肝脏细胞色素P450基因表达的选择性抑制

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The effect of the administration of Thonningia sanguinea (T. S.) on the abundance of individual components of the cytochrome P450 monooxygenase enzyme was examined using Western blotting and competitive reverse-transcriptase-polymerase chain reaction (RT-PCR). We also investigated the time-course of inhibition of T. S. on drug metabolizing enzymes. A single intraperitoneal dose of T. S. extract (5 ml/kg) suppressed CYP, cytochrome b(5) and NADPH-CYP reductase activity by 45%, 34% and 22% respectively 24 h after T. S. adminstration. While T. S. did not have any significant effect on microsomal glutathione S-transferase activity, it inhibited p-nitrophenol hydroxylase (PNPH, CYP2E1) and 7-methoxyresorufin O-demethylase (MROD, CYP1A2) activities by 37% and 32% respectively at 12 h post-T.S. administration. PNPH, erythromycin N-demethylase (ERDM, CYP 3A1/2) and MROD activities were inhibited by 28-36% 24 h after T. S. injection. Consistent with these observations, the levels of CYP2E1, CYP1A2 and CYP3A2 proteins were also suppressed 24 h post-T.S. administration. While CYP2E1 mRNA was unaffected by T. S. administration, CYP1A2 and CYP3A2 mRNAs were decreased by T. S. Cytosolic glutathione S-transferase activity was increased by 30%, 6 h after T. S injection. These data demonstrate that administration of T. S. differentially affect CYP isoforrns in the liver of rats and that T. S. selectively suppresses CYP3A2 and CYP1A2 gene expression. (C) 2003 Elsevier Inc. All rights reserved. [References: 45]
机译：使用蛋白质印迹法和竞争性逆转录酶-聚合酶链反应（RT-PCR）检验了百日红Thonningia sanguinea（T. S.）施用对细胞色素P450单加氧酶的单个成分丰度的影响。我们还研究了抑制T.S.对药物代谢酶的时间过程。腹腔注射单次腹腔注射提取物（5 ml / kg）在施用T.S.后24小时分别抑制CYP，细胞色素b（5）和NADPH-CYP还原酶活性分别为45％，34％和22％。尽管TS对微粒体谷胱甘肽S-转移酶的活性没有任何显着影响，但在12 h时它分别抑制了对硝基苯酚羟化酶（PNPH，CYP2E1）和7-甲氧异纤连蛋白O-脱甲基酶（MROD，CYP1A2）的活性TS后行政。注射T.S.后24小时，PNPH，红霉素N-脱甲基酶（ERDM，CYP 3A1 / 2）和MROD活性被抑制28-36％。与这些观察结果一致，CYP2E1，CYP1A2和CYP3A2蛋白的水平在T.S后24小时也被抑制。行政。虽然CYP2E1 mRNA不受T.S.给药的影响，但CYP1A2和CYP3A2 mRNA却被T.S.降低.T.S注射后6小时，胞质谷胱甘肽S-转移酶活性增加了30％。这些数据表明，T。S.的施用差异影响大鼠肝脏中的CYP异构体，并且T. S.选择性抑制CYP3A2和CYP1A2基因的表达。 （C）2003 Elsevier Inc.保留所有权利。 [参考：45]

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