Ophiopogon japonicus strains from different cultivation regions exhibit markedly different properties on cytotoxicity, pregnane X receptor activation and cytochrome P450 3A4 induction.
Ophiopogon japonicus strains from different cultivation regions exhibit markedly different properties on cytotoxicity, pregnane X receptor activation and cytochrome P450 3A4 induction.
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DOI：
10.3892/br.2015.443
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发表时间：
2015-05
影响因子：
2.3
通讯作者：
Le-Le Ge-Le;Lian-Di Kan;Zhengbing Zhuge;Ke Ma;Shu-qing Chen
中科院分区：
文献类型：
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作者：
Le-Le Ge-Le;Lian-Di Kan;Zhengbing Zhuge;Ke Ma;Shu-qing Chen
麦冬，又名麦冬，是参麦注射液的两个基本成分之一，参麦注射液是一种广泛使用的中药制剂，用于治疗动脉粥样硬化性冠心病和病毒性心肌炎。此前，麦冬乙醇提取物激活了孕烷X受体(PXR)信号通路，诱导了细胞色素P450 3A4(CYP3A4)报告基因，并与由CYP3A4代谢的处方药联合使用，引起了对药物相互作用(HDI)的关注。因此，本研究进一步调查和比较了浙江麦冬(ZM)和川麦冬(CM)两个麦冬品系的乙醇提取物和水提物(ee-和ae-)的差异。采用3-(4，5)-dimethylthiahiazo-(-z-y1)-3，5-diphenytetrazoliumromide法、报告基因分析和逆转录定量聚合酶链式反应检测细胞毒作用、PXR活性和细胞色素P3A4的诱导作用。结果表明，ee-ZM的细胞毒性明显高于ee-CM，PXR激活能力相对较弱，而对细胞色素P3A4的诱导能力明显强于ee-CM。与ae-CM相比，ae-ZM的细胞毒性和细胞色素P3A4的诱导作用仅有轻微差异或无明显差异，而PXR活性明显低于ae-CM。总的来说，不同产地的麦冬在细胞毒性和药物代谢酶诱导作用方面具有不同的性质，应重视将不同产地的麦冬菌株选入中药制剂中，以减少潜在的不良反应和HDI。
Maidong, known as Ophiopogon japonicus, is one of the two basic ingredients of Shenmai injection, which is a widely used herbal preparation in traditional Chinese medicine (TCM) for the treatment of atherosclerotic coronary heart disease and viral myocarditis. Previously, the ethanol extract of Maidong activated the pregnane X receptor (PXR) signaling pathway and induced the cytochrome P450 3A4 (CYP3A4) reporter gene and raised the concern of herb-drug interactions (HDIs) when Maidong was used in combination with prescribed drugs metabolized by CYP3A4. Therefore, the present study further investigated and compared the differences of the ethanol and aqueous extracts (ee- and ae-, respectively) of two Maidong strains, known as Zhe Maidong (ZM) and Chuan Maidong (CM). Cytotoxicity, PXR activation and CYP3A4 induction by the 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-diphenytetrazoliumromide assay, reporter gene assay and reverse transcription-quantitative polymerase chain reaction analysis were examined. The observations showed that ee-ZM demonstrated a significantly higher cytotoxicity, a relatively weaker PXR activation capability and a markedly stronger CYP3A4-inducing capacity than ee-CM. Compared to ae-CM, ae-ZM exhibited only a slight or no difference on cytotoxicity and CYP3A4 induction, while a significant lower level of PXR activation was apparent. Collectively, Maidong from different producing areas possess different properties upon cytotoxicity and the drug-metabolizing enzyme inducing effect, and attention should be paid to the selection of Maidong strains from different planting regions into TCM preparations for reducing potential adverse reactions and HDIs.