非洲豆蔻和三叶豆蔻提取物对细胞色素P450 3A酶的体外和体内抑制作用。

In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melegueta and Denniettia tripetala extracts.

作者信息

Nduka Sunday O, Okonta Mathew J, Ajaghaku Daniel L, Ukwe Chinwe V

机构信息

Department of Clinical Pharmacy and Pharmacy Management, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.

Department of Clinical Pharmacy and Pharmacy Management, University of Nigeria, Nsukka, Enugu State, Nigeria.

出版信息

Asian Pac J Trop Med. 2017 Jun;10(6):576-581. doi: 10.1016/j.apjtm.2017.06.006. Epub 2017 Jun 16.

DOI:10.1016/j.apjtm.2017.06.006

PMID:28756922

Abstract

OBJECTIVE

To evaluate the in vitro and in vivo inhibitory effects of two commonly used herbs, Aframomum melegueta (A. melengueta) and Dennettia tripetala (D. tripetala) on CYP 3A enzymes.

METHODS

In vitro inhibition of the enzymes were assessed with microsomes extracted from female albino rats using erythromycin-N-demethylation assay (EMND) method while their in vivo effects were measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic parameters were determined using non-compartmental analysis as implemented in WinNonlin pharmacokinetic program.

RESULTS

EMND assay with intestinal microsomes indicated that aqueous extracts of D. tripetala and A. melengueta significantly (P < 0.05) inhibited intestinal CYP 3A activity at both 50 μg and 100 μg concentrations. Petroleum ether extract of D. tripetala and ethanol extracts of A. melengueta inhibited intestinal CYP3A activity at 100 μg but not at 50 μg concentrations. All the extracts showed an in vitro dose dependent CYP 3A inhibition with liver microsomes. In vivo analysis showed that pre-treatment with the extracts enhanced systemic absorption of simvastatin with reductions in metabolizing enzymes activity as indicated in significant increases in maximal concentration, area under curve, area under moment curve and mean resident time of simvastatin (P < 0.05).

CONCLUSIONS

Herbal preparations containing these plants' extracts should be used with caution especially in patients on CYP450 3A substrate medications.

摘要

目的

评估两种常用草药——非洲豆蔻（Aframomum melegueta）和三瓣丹尼亚藤（Dennettia tripetala）对CYP 3A酶的体外和体内抑制作用。

方法

采用红霉素-N-去甲基化试验（EMND）方法，用从雌性白化大鼠提取的微粒体评估酶的体外抑制作用，同时通过测定大鼠体内辛伐他汀血浆浓度来衡量其体内作用。使用WinNonlin药代动力学程序中实施的非房室分析确定药代动力学参数。

结果

肠道微粒体的EMND试验表明，三瓣丹尼亚藤和非洲豆蔻的水提取物在50μg和100μg浓度下均显著（P < 0.05）抑制肠道CYP 3A活性。三瓣丹尼亚藤的石油醚提取物和非洲豆蔻的乙醇提取物在100μg浓度下抑制肠道CYP3A活性，但在50μg浓度下无此作用。所有提取物对肝微粒体均显示出体外剂量依赖性的CYP 3A抑制作用。体内分析表明，提取物预处理可增强辛伐他汀的全身吸收，代谢酶活性降低，表现为辛伐他汀的最大浓度、曲线下面积、矩曲线下面积和平均驻留时间显著增加（P < 0.05）。