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异木患叶水提取物对细胞色素P450和ABCB1/ P-糖蛋白活性的体外调节作用

In vitro modulation of the cytochrome P450 and ABCB1/P-glycoprotein activities of the aqueous extract of Allophylus cominia (L) Sw. leaves.

作者信息

Pérez Carlos L, Donato Maria T, Hernández Ivones, Paz Lopes Miriam T, Marrero Evangelina, Herrera Jose A, Gómez-Lechón Maria J, Rodeiro Idania

机构信息

Departamento de Bioquímica, Instituto de Ciencias Básicas y Preclínicas Victoria de Girón (ICBP), Universidad de Ciencias Médicas de La Habana (UCMH), La Habana, Cuba.

Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain.

出版信息

Drug Metab Pers Ther. 2017 Dec 20;32(4):201-208. doi: 10.1515/dmpt-2017-0020.

Abstract

BACKGROUND

The aqueous extract of the Allophylus cominia (L) Sw (Sapindaceae) leaves has shown anti-diabetic, anti-obesity and anti-inflammatory properties. In the Caribbean region, it is typically used for the treatment of type-2 diabetes.

METHODS

Considering the herb-drug interaction, the aim of this study was to evaluate the potential effects of the A. cominia extract on the cytochrome P450 (CYP) (rat hepatocyte model) and P-glycoprotein (P-gp) (4T1 cell line) systems.

RESULTS

The extract did not decrease the cell viability after being assayed by the MTT test at up to 1500 μg/mL for 72 h. The exposure of the cultured rat hepatocytes to the product (up to 250 μg/mL) for 48 h increased the activities of CYP-1A2, 2C9, and 2E1 by 1.46-, 1.60-, and 1.51-fold, respectively, compared with the controls. The activities of CYP-2B6, 2D6, and 3A4 were not significantly altered, whereas the activity of P-gp decreased by 2- and 4-fold. In addition, the extracts at 100 and 200 μg/mL significantly increased doxorubicin cytotoxicity in these cells 24 h after treatment.

CONCLUSIONS

The findings indicate that the A. cominia extract modulates the CYP and P-gp systems increasing sensitivity to doxorubicin. Further studies are necessary to evaluate the potential herb-drug interaction or chemosensitive properties.

摘要

背景

异木患(无患子科)叶的水提取物已显示出抗糖尿病、抗肥胖和抗炎特性。在加勒比地区,它通常用于治疗2型糖尿病。

方法

考虑到草药与药物的相互作用,本研究的目的是评估异木患提取物对细胞色素P450(CYP)(大鼠肝细胞模型)和P-糖蛋白(P-gp)(4T1细胞系)系统的潜在影响。

结果

通过MTT试验检测,提取物在高达1500μg/mL的浓度下作用72小时后,并未降低细胞活力。与对照组相比,培养的大鼠肝细胞在48小时内暴露于该产物(高达250μg/mL)后,CYP-1A2、2C9和2E1的活性分别增加了1.46倍、1.60倍和1.51倍。CYP-2B6、2D6和3A4的活性没有显著改变,而P-gp的活性降低了2倍和4倍。此外,在处理24小时后,100和200μg/mL的提取物显著增加了这些细胞中阿霉素的细胞毒性。

结论

研究结果表明,异木患提取物调节CYP和P-gp系统,增加对阿霉素的敏感性。有必要进一步研究以评估潜在的草药与药物相互作用或化学敏感性特性。

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