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首页> 外文期刊>Life sciences >Modulation of drug-metabolizing enzymes by extracts of a herbal medicine Evodia rutaecarpa in C57BL/6J mice.
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Modulation of drug-metabolizing enzymes by extracts of a herbal medicine Evodia rutaecarpa in C57BL/6J mice.

机译：草药Evodia rutaecarpa提取物对C57BL / 6J小鼠的药物代谢酶的调节。

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Evodia rutaecarpa is a traditional Chinese medicine used for the treatment of gastrointestinal disorders and headache. To assess the possible drug interactions, effects of methanol and aqueous extracts of E. rutaecarpa on drug-metabolizing enzymes, cytochrome P450 (CYP), UDP-glucuronosyl transferase (UGT), and glutathione S-transferase (GST) were studied in C57BL/6J mice. Treatment of mice with methanol extract by gastrogavage caused a dose-dependent increase of liver microsomal 7-ethoxyresorufin O-deethylation (EROD) activity. In liver, methanol extract at 2 g/kg caused 47%, 7-, 8-, 4-fold, 81% and 26% increases of benzo(a)pyrene hydroxylation (AHH), EROD, 7-methoxyresorufin O-demethylation (MROD), 7-ethoxycoumarin O-deethylation (ECOD), benzphetamine N-demethylation, and N-nitrosodimethylamine N-demethylation activities, respectively. Aqueous extract at 2 g/kg caused 68%, 2-fold, and 83% increases of EROD, MROD, and ECOD activities, respectively. For conjugation activities, methanol extract elevated UGT and GST activities. Aqueous extract elevated UGT activity without affecting GST activity. Immunoblot analyses showed that methanol extract increased the levels of CYP1A1, CYP1A2, CYP2B-, and GSTYb-immunoreactive proteins. Aqueous extract increased CYP1A2 protein level. In kidney, both extracts had no effects on AHH, ECOD, UGT, and GST activities. Three major bioactive alkaloids rutaecarpine, evodiamine, and dehydroevodiamine were present in both extracts. These alkaloids at 25 mg/kg increased hepatic EROD activity. These results demonstrated that E. rutaecarpa methanol and aqueous extracts could affect drug-metabolizing enzyme activities. Rutaecarpine, evodiamine, and dehydroevodiamine contributed at least in part to the increase of hepatic EROD activity by extracts of E. rutaecarpa. Thus, caution should be paid to the possible drug interactions of E. rutaecarpa and CYP substrates.
机译：吴茱carp是治疗胃肠道疾病和头痛的传统中药。为了评估可能的药物相互作用，在C57BL / 6J小鼠。用胃灌胃法用甲醇提取物治疗小鼠会引起肝脏微粒体7-乙氧基间苯二酚O-脱乙基（EROD）活性的剂量依赖性增加。在肝脏中，以2 g / kg的甲醇提取物引起的苯并（a）re羟基化（AHH），EROD，7-甲氧基异鲁布芬O-脱甲基化（ MROD），7-乙氧基香豆素O-去乙基化（ECOD），苯丙胺N-去甲基化和N-亚硝基二甲胺N-去甲基化活性。 2 g / kg的水提物分别导致EROD，MROD和ECOD活性增加68％，2倍和83％。对于共轭活性，甲醇提取物可提高UGT和GST活性。水性提取物在不影响GST活性的情况下提高了UGT活性。免疫印迹分析表明，甲醇提取物可提高CYP1A1，CYP1A2，CYP2B-和GSTYb免疫反应蛋白的水平。水提取物增加CYP1A2蛋白水平。在肾脏中，两种提取物均对AHH，ECOD，UGT和GST活性没有影响。两种提取物中均存在三种主要的生物活性生物碱，如芸香芸香碱，依夫二胺和脱氢依夫二胺。这些以25 mg / kg的生物碱增加了肝脏EROD活性。这些结果表明，大果E甲醇和水提物可能影响药物代谢酶的活性。 Rutaecarpine，evodiamine和dehydroevodiamine至少部分地导致了rutaecarpa提取物对肝脏EROD活性的增加。因此，应谨慎对待大果肠衣和CYP底物可能的药物相互作用。

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