对草药多药的影响:香豆素诱导的肝毒性通过常见的草药植物化学物质黄芪甲苷IV和白术内酯I增加

IF 2.8 4区 医学 Q2 TOXICOLOGY
Susan M. Britza, I. Musgrave, R. Byard
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引用次数: 3

摘要

摘要肝毒性是许多物质的一种众所周知的不良反应,其毒性通常是由药物与其他类药物的相互作用引起的。随着包括草药在内的补充和替代药物的供应增加,药物与草药中的类药物之间发生不良相互作用的可能性增加。然而,人们对潜在的中草药相互作用的影响知之甚少。为了评估许多草药中常见的两种细胞色素P450酶调节植物化学物质,白术内酯I(ATR-I)和黄芪甲苷IV(AST-IV)与许多食物中常见的另一种植物化学物质香豆素相互作用的潜力,将肝癌细胞系HepG2的肝细胞功能模型暴露于这些药物中。为了确定这些植物化学物质对细胞色素P450的调节作用,用利福平诱导某些细胞诱导细胞色素P450%。增加ATR-I的浓度与固定无毒浓度的香豆素(200 µM),表现出显著的添加剂相互作用。300 µM ATR-I使细胞活力降低31%(p  0.05)。这些结果证明了常见中草药植物化学物质的潜在毒性相互作用能力,并强调了香豆素介导的毒性的潜在重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Implications for herbal polypharmacy: coumarin-induced hepatotoxicity increased through common herbal phytochemicals astragaloside IV and atractylenolide I
Abstract Hepatotoxicity is a well-known adverse effect of many substances, with toxicity often resulting from interactions of drugs with other drug-like substances. With the increased availability of complementary and alternative medicines, including herbal medicines, the likelihood of adverse interactions between drugs and drug-like substances in herbs increases. However, the impact of potential herb-herb interactions is little understood. To assess the potential of two cytochrome P450 enzyme modulating phytochemicals common to many herbal medicines, atractylenolide I (ATR-I) and astragaloside IV (AST-IV), to interact with coumarin, another phytochemical common in many foods, a hepatocyte function model with a liver carcinoma cell line, HepG2, was exposed to these agents. To determine the effects of cytochrome P450 modulation by these phytochemicals certain cells were induced with rifampicin to induce cytochrome P450. Increasing concentrations of ATR-I combined with a fixed, nontoxic concentration of coumarin (200 µM), demonstrated significant additive interactions. 300 µM ATR-I produced a 31% reduction in cell viability (p < 0.01) with coumarin in rifampicin uninduced cells. In rifampicin-induced cells, ATR-I (100–300 µM) produced a significant reduction in cell viability (p < 0.01) with coumarin (200 µM). AST-IV with fixed coumarin (200 µM) showed 27% toxicity at 300 µM AST-IV in rifampicin uninduced cells (p < 0.05) and 30% toxicity in rifampicin induced cells (p < 0.05). However, when fixed coumarin and AST-IV were combined with increasing concentrations of ATR-I no further significant increase in toxicity was observed (p > 0.05). These results demonstrate the potential toxic interactive capabilities of common traditional Chinese herbal medicine phytochemicals and underline the potential importance of coumarin-mediated toxicity.
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来源期刊
自引率
3.10%
发文量
66
期刊介绍: Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.
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