Department of Biological Pharmaceutics, School of Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
J Ethnopharmacol. 2012 Oct 31;144(1):33-8. doi: 10.1016/j.jep.2012.08.020. Epub 2012 Sep 4.
In Chinese medicine clinics, traditional Chinese herbs are used to treat disorders of Yin and Yang balance, including Kidney-Yang Deficiency. The activity of the hepatic cytochrome P450 3A (CYP3A) is closely associated with body status. The aim of the present study is to investigate CYP3A enzymatic activity and CYP3A4 protein expression using a Kidney-Yang Deficiency rat model and furthermore to investigate the intervention effects of the Pungent-hot herb Xian Mao. This work contributes rationale for personalized medicine and enhances our understanding of herb-drug interactions.
Rats were randomly divided into three groups: the model group, the Xian Mao group and the intervention group (model rats treated with Xian Mao). The model rats were given an intramuscular injection of hydrocortisone for 14 days, and the control rats were given normal saline. The Xian Mao group consisted of normal rats treated with Xian Mao by oral gavage for 7 days. The intervention group was given Xian Mao for 7 days after treatment with hydrocortisone. The activity of CYP3A was detected by using the erythromycin-N-demethylase method. CYP3A4 protein expression level was detected by Western-blot.
CYP3A enzymatic activity in the Kidney-Yang Deficiency rat was decreased by 44% compared to normal animals. The relative CYP3A4 protein expression level of the Kidney-Yang Deficiency rat (mean value 0.663±0.188) was 20% lower than that of normal rat (0.830±0.199). The in vitro data showed that CYP3A activity was significantly (P<0.001) inhibited (decreased by 59%) by Xian Mao concentrations of 1mg/mL. The in vivo data also showed that CYP3A activity was significantly decreased in the rats treated with the three doses of Xian Mao. The CYP3A4 protein expression was significantly decreased by Xian Mao treatment at the high and intermediate doses (30 and 20 g/kg, respectively) compared with the normal group. However, the intervention group (the Kidney-Yang Deficiency rat treated with Xian Mao at 20 and 30 g/kg) showed an increased CYP3A activity and CYP3A4 protein expression compared with the herb-untreated model rats.
CYP3A enzymatic activity and CYP3A4 protein expression could be inhibited by Xian Mao. The CYP3A activity and CYP3A4 expression in the Kidney-Yang Deficiency model rat were lower than that of normal rat but this deficiency could be rescued by treatment with Xian Mao.
在中医诊所中，使用中药来治疗阴阳失衡的疾病，包括肾阳虚。肝微粒体 CYP3A（CYP3A）的活性与身体状况密切相关。本研究旨在通过肾阳虚大鼠模型来研究 CYP3A 酶活性和 CYP3A4 蛋白表达，并进一步研究辛荑的干预作用。这项工作为个体化医学提供了依据，并加深了我们对草药-药物相互作用的理解。
大鼠随机分为三组：模型组、辛荑组和干预组（模型大鼠用辛荑治疗）。模型大鼠给予肌肉注射氢化可的松 14 天，对照组大鼠给予生理盐水。辛荑组给予正常大鼠辛荑灌胃 7 天。干预组在氢化可的松治疗后给予辛荑 7 天。CYP3A 活性采用红霉素-N-脱甲基酶法检测。CYP3A4 蛋白表达水平采用 Western-blot 检测。
与正常动物相比，肾阳虚大鼠 CYP3A 酶活性降低了 44%。肾阳虚大鼠 CYP3A4 蛋白表达水平相对值（平均值 0.663±0.188）比正常大鼠低 20%（0.830±0.199）。体外数据显示，辛荑浓度为 1mg/mL 时，CYP3A 活性显著（P<0.001）抑制（降低 59%）。体内数据还显示，辛荑高、中剂量（30 和 20 g/kg）处理的大鼠 CYP3A 活性明显降低。与正常组相比，辛荑处理后 CYP3A4 蛋白表达在高剂量（30 g/kg）和中剂量（20 g/kg）时明显降低。然而，与未用草药治疗的模型大鼠相比，干预组（肾阳虚大鼠用辛荑 20 和 30 g/kg 治疗）的 CYP3A 活性和 CYP3A4 蛋白表达增加。
辛荑可抑制 CYP3A 酶活性和 CYP3A4 蛋白表达。肾阳虚模型大鼠 CYP3A 活性和 CYP3A4 表达低于正常大鼠，但用辛荑治疗可挽救这种缺陷。
