Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy.
Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy.
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巴布亚新几内亚药用植物提取物与抗逆转录病毒疗法的相互作用。
DOI：
10.1016/j.jep.2014.07.023
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发表时间：
2014
影响因子：
5.4
通讯作者：
Franklin,MichaelR
中科院分区：
文献类型：
--
作者：
Larson,EricaC;Hathaway,LauraB;Lamb,JohnG;Pond,ChrisD;Rai,PremP;Matainaho,TeatulohiK;Piskaut,Pius;Barrows,LouisR;Franklin,MichaelR
民族药理学相关性 巴布亚新几内亚 (PNG) 很大一部分人口感染人类免疫缺陷病毒 (HIV)。治疗需要终生使用抗逆转录病毒疗法（ART）。巴布亚新几内亚的大多数人使用从植物中提取的传统药物 (TM) 进行各种类型的健康促进。因此，人们担心草药与药物的相互作用可能会影响 ART 的疗效。草药与药物或药物与药物之间的相互作用通过两种主要机制发生在代谢水平：酶诱导或酶抑制。在本研究中，筛选了巴布亚新几内亚常用药用植物提取物中与细胞色素 P450 (CYP) 相关的草药-药物相互作用。材料和方法利用市售的基于细胞的荧光素酶报告系统，筛选了 69 种 TM 植物的甲醇提取物，以确定其通过人芳烃受体 (hAhR-) 和人孕烷 X 受体 (hPXR-) 依赖性机制诱导 CYP 的能力。使用人肝微粒体和酶选择性模型底物测定了三种主要 CYP（CYP1A2、CYP3A4 和 CYP2D6）的抑制作用。结果几乎三分之一的 TM 植物提取物诱导了 CYP1A2 的 hAhR 依赖性表达、CYP3A4 的 hPXR 依赖性表达，或两者兼而有之。几乎三分之二抑制 CYP1A2、CYP3A4 或 CYP2D6 或其组合。许多植物提取物同时表现出诱导和抑制特性。结论我们证明，巴布亚新几内亚药用植物提取物通过诱导和/或抑制影响药物代谢酶的有效和选择性能力是一种常见现象。传统药物与抗逆转录病毒疗法同时使用可能会显着改变体内抗逆转录病毒药物的浓度；及其功效。鉴于这种后果，巴布亚新几内亚医疗保健提供者应该为艾滋病毒患者提供咨询。
Ethnopharmacological relevanceA substantial proportion of the population in Papua New Guinea (PNG) lives with human immunodeficiency virus (HIV). Treatment requires lifelong use of antiretroviral therapy (ART). The majority of people in PNG use traditional medicines (TM) derived from plants for all types of health promotions. Consequently, there is a concern that herb–drug interactions may impact the efficacy of ART. Herb–drug, or drug–drug, interactions occur at the level of metabolism through two major mechanisms: enzyme induction or enzyme inhibition. In this study, extracts of commonly-used medicinal plants from PNG were screened for herb–drug interactions related to cytochrome P450s (CYPs).Materials and methodsSixty nine methanol extracts of TM plants were screened for their ability to induce CYPs by human aryl hydrocarbon receptor- (hAhR-) and human pregnane X receptor- (hPXR-) dependent mechanisms, utilizing a commercially available cell-based luciferase reporter system. Inhibition of three major CYPs, CYP1A2, CYP3A4, and CYP2D6, was determined using human liver microsomes and enzyme-selective model substrates.ResultsAlmost one third of the TM plant extracts induced the hAhR-dependent expression of CYP1A2, the hPXR-dependent expression of CYP3A4, or both. Almost two thirds inhibited CYP1A2, CYP3A4, or CYP2D6, or combinations thereof. Many plant extracts exhibited both induction and inhibition properties.ConclusionsWe demonstrated that the potent and selective ability of extracts from PNG medicinal plants to affect drug metabolizing enzymes through induction and/or inhibition is a common phenomenon. Use of traditional medicines concomitantly with ART could dramatically alter the concentrations of antiretroviral drugs in the body; and their efficacy. PNG healthcare providers should counsel HIV patients because of this consequence.