UHPLC-MS/MS standardized extract of Vernonia amygdalina leaf inhibits CYP2C9 and CYP3A4 activities in hepatic cells of control and streptozotocin-induced diabetic rats.
Bassel Al Sabbagh, Vijayaraj Kumar Palanirajan, Yik-Ling Chew, Jin Han Chin, Mariam Ahmad, Gabriel Akyirem Akowuah
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Abstract
Objectives: Vernonia amygdalina Del. is a perennial tropical shrub from Asteraceae. The fresh leaf of V. amygdalina 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 V. amygdalina. The study also aims to investigate the effects of the aqueous leaf extract of V. amygdalina 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 V. amygdalina leaf extract. The inhibitory effect of the extract suggests that concomitant use of V. amygdalina leaf preparations with conventional drugs metabolized and eliminated from the body by CYP3A4 and CYP2C9 enzymes may lead to possible interaction.
目的：苦杏仁。是一种来自菊科的多年生热带灌木。由于其药用和营养特性，苦杏仁的新鲜叶子被作为蔬菜食用。本研究主要对苦杏仁叶水提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 -葡萄糖醛酸和1,5- o -二咖啡酰奎宁酸进行了定量分析。研究苦杏仁叶水提物对对照和糖尿病大鼠肝细胞细胞色素P450 2C9 （CYP2C9）和细胞色素P450 3A4 （CYP3A4）的影响。方法：采用超高效液相色谱-多反应监测串联质谱（UHPLC-MS/MS-MRM）技术对活性成分进行定量分析。根据制造商的说明，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：对三种活性物质进行了定量检测。结果表明，木犀草素-7- o -葡糖苷含量最高（47 μg/mg），其次是木犀草素-7- o -葡糖苷（3.5 μg/mg）和1,5- o -二咖啡酰奎宁酸（1.07 μg/mg）。该提取物对糖尿病大鼠CYP3A4和CYP2C9酶活性均有抑制作用。结论：UHPLC-MS/MS-MRM方法灵敏、可靠，可用于苦杏仁叶提取物的质量控制。该提取物的抑制作用表明，苦杏仁叶制剂与经CYP3A4和CYP2C9酶代谢并从体内排出的常规药物同时使用可能会导致相互作用。
期刊介绍：
Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.
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