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叶的超高效液相色谱-串联质谱标准化提取物抑制对照大鼠和链脲佐菌素诱导的糖尿病大鼠肝细胞中CYP2C9和CYP3A4的活性。

UHPLC-MS/MS standardized extract of leaf inhibits CYP2C9 and CYP3A4 activities in hepatic cells of control and streptozotocin-induced diabetic rats.

作者信息

Sabbagh Bassel Al, Palanirajan Vijayaraj Kumar, Chew Yik-Ling, Chin Jin Han, Ahmad Mariam, Akowuah Gabriel Akyirem

机构信息

Faculty of Pharmaceutical Sciences, UCSI University, Cheras, Kuala Lumpur, Malaysia.

Faculty of Medicine, MAHSA University, Kuala Langat, Selangor, Malaysia.

出版信息

Drug Metab Pers Ther. 2024 Dec 12;39(4):231-241. doi: 10.1515/dmpt-2024-0005. eCollection 2024 Dec 1.

DOI:10.1515/dmpt-2024-0005
PMID:39658558
Abstract

OBJECTIVES

Del. is a perennial tropical shrub from Asteraceae. The fresh leaf of is consumed as a vegetable due to its medicinal and nutritional properties. The present study focused on the quantification of bioactive compounds, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, and 1,5-O-dicaffeoylquinic acid from aqueous leaf extract of The study also aims to investigate the effects of the aqueous leaf extract of on cytochrome P450 2C9 (CYP2C9), and cytochrome P450 3A4 (CYP3A4) in hepatic cells of control and diabetic rats.

METHODS

The quantification of the bioactive compounds was conducted using ultra-high-performance liquid chromatography multiple reactions monitoring tandem mass spectrometry (UHPLC-MS/MS-MRM) technique. The effect of the extract on CYP2C9 and CYP3A4 activities was determined using a fluorometric screening kit according to the manufacturer's instructions.

RESULTS

The three bioactive compounds were detected and quantified in the aqueous leaf extract. Results showed that the content of luteolin-7-O-glucuronide (47 μg/mg) was the highest followed by luteolin-7-O-glucoside (3.5 μg/mg) and 1,5-O-dicaffeoylquinic acid (1.07 μg/mg). The extract showed an inhibitory effect on CYP3A4 and CYP2C9 enzyme activities in control and diabetic rats.

CONCLUSIONS

The UHPLC-MS/MS-MRM method is sensitive and reliable for the quality control of leaf extract. The inhibitory effect of the extract suggests that concomitant use of leaf preparations with conventional drugs metabolized and eliminated from the body by CYP3A4 and CYP2C9 enzymes may lead to possible interaction.

摘要

目的

Del.是菊科的一种多年生热带灌木。因其药用和营养特性,其新鲜叶子被当作蔬菜食用。本研究聚焦于对Del.水叶提取物中生物活性化合物木犀草素-7-O-葡萄糖苷、木犀草素-7-O-葡萄糖醛酸苷和1,5-O-二咖啡酰奎宁酸进行定量分析。该研究还旨在调查Del.水叶提取物对正常和糖尿病大鼠肝细胞中细胞色素P450 2C9(CYP2C9)和细胞色素P450 3A4(CYP3A4)的影响。

方法

使用超高效液相色谱多反应监测串联质谱(UHPLC-MS/MS-MRM)技术对生物活性化合物进行定量分析。根据制造商说明,使用荧光筛选试剂盒测定提取物对CYP2C9和CYP3A4活性的影响。

结果

在水叶提取物中检测并定量了这三种生物活性化合物。结果显示木犀草素-7-O-葡萄糖醛酸苷含量最高(47μg/mg),其次是木犀草素-7-O-葡萄糖苷(3.5μg/mg)和1,5-O-二咖啡酰奎宁酸(1.07μg/mg)。该提取物对正常和糖尿病大鼠的CYP3A4和CYP2C9酶活性均表现出抑制作用。

结论

UHPLC-MS/MS-MRM方法对于Del.叶提取物的质量控制灵敏且可靠。提取物的抑制作用表明Del.叶制剂与通过CYP3A4和CYP2C9酶在体内代谢和消除的传统药物同时使用可能会导致相互作用。

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