Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs

Fei SONG; Jian YANG; Chun WANG; Xia WANG; Wei-wei LI; Jie PAN; Yan-yu LAN; Ting LIU

doi:10.13422/j.cnki.syfjx.20181905

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Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs

Pharmacology | 更新时间：2021-02-09

- Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 2, Pages: 60-67(2019)
- 作者机构：
  
  贵州医科大学　药用植物功效与利用国家重点实验室，贵州省药物制剂重点实验室，民族药与中药开发应用教育部工程研究中心，药学院，贵阳　 550004
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20181905
  CLC： R22; R285; R969.1; R284; R945; O657.6
- Received：04 April 2018，
  
  Published Online：12 July 2018，
  
  Published：20 January 2019
- 稿件说明：
移动端阅览
Fei SONG, Jian YANG, Chun WANG, et al. Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(2): 60-67.
DOI：

Fei SONG, Jian YANG, Chun WANG, et al. Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(2): 60-67. DOI： 10.13422/j.cnki.syfjx.20181905.

摘要

目的：

采用Cocktail探针药物法考察羊耳菊活性部位提取物(以下均简称为羊耳菊)对6种大鼠细胞色素P450(CYP450)主要亚型酶活性的影响。

方法：

羊耳菊高、低剂量组大鼠给药剂量分别为8.127，2.709 g·kg

－1

·d

－1

(以生药量计算)，分别连续灌胃7，14 d后尾静脉注射Cocktail探针药物咖啡因、咪达唑仑、甲苯磺丁脲、奥美拉唑、美托洛尔和氯唑沙宗，不同时间点采集血样，建立超高效液相串联质谱法(UPLC-MS)测定大鼠血浆中6种探针药物的浓度，运用DAS 2.0软件计算其药动学参数，以考察羊耳菊在大鼠体内对CYP1A2，CYP3A，CYP2C9，CYP2C19，CYP2D6，CYP2E1这6种亚型酶代谢活性的影响。

结果：

与空白组相比，奥美拉唑指标下，给药组的药时曲线下面积AUC

和AUC

0-∞

增大，14 d给药组的半衰期(

1/2

)增大，清除率(CL)降低；甲苯磺丁脲指标下，14 d高剂量组的AUC

，AUC

0-∞

和

1/2

增大；咖啡因指标下，给药组的

1/2

明显增大，14 d给药组的AUC

和AUC

0-∞

增大而CL降低；但以上3个指标的表观分布容积(

)均无明显变化。与空白组相比，咪达唑仑指标下，除7 d低剂量组之外，其他给药组的AUC

，AUC

0-∞

和

1/2

明显增大，CL明显降低，

增大；氯唑沙宗和美托洛尔的药动学参数与空白组相比差异没有显著性。

结论：

羊耳菊对大鼠肝药酶CYP3A，CYP1A2，CYP2C9和CYP2C19的活性具有不同程度的抑制作用，其中对CYP3A的抑制作用最强。

Abstract

Objective:

To study on the effect of

Inula cappa

extract on the activities of six cytochrome P450(CYP450) enzymes in rats by Cocktail probe method.

Method:

Rats in the

cappa

high and low dose groups were given oral administration of active fractions of

cappa

at a dose of 8.127

2.709 g·kg

-1

·d

-1

of the material for 7

14 d

repectively.Probe drugs(caffeine

midazolam

tolbutamide

omeprazole

metoprolol

chlorzoxazone) were simultaneously injected to rats after administration.Plasma was collected at different time after the administration of probe drugs.The plasma concentrations of these six probes were measured by UPLC-MS and their corresponding pharmacokinetic parameters were calculated with DAS 2.0.

Result:

Compared with the control group

only the apparent volume of distribution(

) of midazolam was increased; area under the curve(AUC

and AUC

0-∞

)and half-life period(

1/2

) of caffeine

midazolam

tolbutamide and omeprazole were increased and the clearance rate(CL) of them was decreased in rats of

cappa

groups.But there were no differences in pharmacokinetic parameters of chlorzoxazone and metoprolol.

Conclusion:

capp

a can reduce the enzymatic activities of CYP3A

CYP1A2

CYP2C9 and CYP2C19 in rats at different degree

among which CYP3A is the strongest.

关键词

Keywords

references

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