Herba Gelsemii elegantis is detoxified by ramulus et folium Mussaendae pubescentis extract by modulating hepatic cytochrome P450 and glutathione S-transferase enzymes in rats.
Herba Gelsemii elegantis is detoxified by ramulus et folium Mussaendae pubescentis extract by modulating hepatic cytochrome P450 and glutathione S-transferase enzymes in rats.
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玉蜀黍叶提取物通过调节大鼠肝细胞色素 P450 和谷胱甘肽 S-转移酶来解毒。
DOI：
10.3892/etm.2017.5351
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发表时间：
2018-01
影响因子：
2.7
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Wang Y;Wu S;Liu C;Lu X;Chen Z
钩吻（HerbaGelsemielegantis，GE）是我国民间常用中药，但具有较高的急性毒性。在传统的中药中，玉叶金花（MP）可以解毒，但其解毒机制仍不清楚。本研究旨在评估MP调节GE在大鼠中的作用的解毒机制，包括抑制肝细胞色素P（CYP）450和谷胱甘肽S-转移酶（GST）。雄性Sprague道利大鼠经口给予三种剂量（0.36、0.43或0.54 g/kg）的GE单独给药，并以最高剂量与MP（21.6 g/kg）联合给药，每天一次，连续7天。对照组动物接受相同体积的生理盐水。采用逆转录定量聚合酶链反应（RT-qPCR）、免疫印迹和免疫组化方法分别检测肝脏CYP 2 E1和CYP 1A 2亚家族的mRNA和蛋白表达。采用RT-qPCR、Western blot和比色法分别检测肝脏GST的mRNA和蛋白表达以及酶活性。结果表明，GE可显著抑制CYP 2 E1 mRNA和蛋白的表达，且呈剂量依赖性。与高剂量GE单独给药相比，MP联合给药可增加CYP 2 E1 mRNA和蛋白表达。通过免疫组化染色，在清晰的背景下，位于肝血管丛周围的表达CYP 2 E1的细胞被鉴定。CYP 1A 2的结果与CYP 2 E1的结果相似。在所有浓度下，与对照组相比，GE以剂量依赖的方式显著抑制GST mu 1（GSTm 1）mRNA和蛋白表达。与高剂量GE相比，GE和MP联合应用可增加GSTm 1的mRNA和蛋白表达。GE组与GE + MP组GST-pi mRNA和蛋白表达差异无统计学意义。值得注意的是，与MP共处理的大鼠显著免受GE产生的GST活性降低的影响。目前的研究表明，GE和MP的共同管理上调CYP 450和GST酶的活性时，与GE单独相比。这种调节作用可以解释MP降低GE急性毒性的作用。
Herba Gelsemii elegantis (GE) has been frequently used as a Chinese folk medicine but has high acute toxicity. In Traditional Chinese Medicine, it may be detoxified by Ramulus et Folium Mussaendae pubescentis (MP), but the detoxification mechanism has remained elusive. The present study aimed to evaluate the detoxification mechanisms by which MP modulates the effect of GE in rats, including the inhibition of hepatic cytochrome P (CYP)450 and glutathione S-transferase (GST) enzymes. Male Sprague Dawley rats were orally administered GE at three doses (0.36, 0.43 or 0.54 g/kg) alone and, at the highest dose, in combination with MP (21.6 g/kg) every day for 7 consecutive days. The control group of animals received the same volume of saline. The mRNA and protein expression of hepatic CYPs representative of two subfamilies (CYP2E1 and CYP1A2) were separately assessed by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), western blot and immunohistochemistry assays. The mRNA and protein expression as well as enzyme activity of hepatic GST were assessed by RT-qPCR, western blot and colorimetric assays, respectively. The results indicated that GE significantly inhibited CYP2E1 mRNA and protein expression in a dose-dependent manner. Co-administration of MP increased CYP2E1 mRNA and protein expression as compared with the high GE dose alone. Cells expressing CYP2E1, located around the hepatic vascular plexus under a clear background, were identified by immunohistochemical staining. The results for CYP1A2 were similar to those for CYP2E1. At all concentrations used, GE significantly inhibited GST mu 1 (GSTm1) mRNA and protein expression in a dose-dependent manner, as compared with the control. Combination of GE and MP increased the mRNA and protein expression of GSTm1 as compared with the high dose of GE. However, the differences in GST-pi mRNA and protein expression between the GE and GE + MP groups were not significant. Of note, rats co-treated with MP were significantly protected from the decrease in GST activity produced by GE. The present study indicated that co-administration of GE and MP upregulated the activities of CYP450 and GST enzymes when compared with GE alone. This modulation may explain for the effect of MP in reducing the acute toxicity of GE.
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影响因子：
3.3
作者：
Dourado, Daniel F. A. R.;Fernandes, Pedro Alexandrino;Ramos, Maria Joao
通讯作者：
Ramos, Maria Joao
影响因子：
3.8
作者：
Gallagher, EP;Kunze, KL;Eaton, DL
通讯作者：
Eaton, DL
影响因子：
13.5
作者：
Bradford, BU;Kono, H;Rusyn, I
通讯作者：
Rusyn, I
钩吻生物碱 koumine 对炎症和神经病理性疼痛模型的影响以及四氢孕酮的可能机制
影响因子：
3.6
作者：
Xu, Ying;Qiu, Hong-Qiang;Yu, Chang-Xi
通讯作者：
Yu, Chang-Xi
DOI：
10.1016/s1383-5718(99)00167-9
发表时间：
2000-01-03
影响因子：
1.9
作者：
Autrup, H
通讯作者：
Autrup, H