Influence of Wutoutang Adding Different Processed Products of Pinelliae Rhizoma on CYP3A in Rats

CHENG Zai-xing; CHEN Hong; WU Jin-jun; LIN Na

doi:10.13422/j.cnki.syfjx.2017200090

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Influence of Wutoutang Adding Different Processed Products of Pinelliae Rhizoma on CYP3A in Rats

更新时间：2024-01-04

- Influence of Wutoutang Adding Different Processed Products of Pinelliae Rhizoma on CYP3A in Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 23, Issue 20, Pages: 90-95(2017)
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- DOI：10.13422/j.cnki.syfjx.2017200090
  CLC： R285.5
- Published：2017
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CHENG Zai-xing, CHEN Hong, WU Jin-jun, et al. Influence of Wutoutang Adding Different Processed Products of Pinelliae Rhizoma on CYP3A in Rats[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(20): 90-95.
DOI：

CHENG Zai-xing, CHEN Hong, WU Jin-jun, et al. Influence of Wutoutang Adding Different Processed Products of Pinelliae Rhizoma on CYP3A in Rats[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(20): 90-95. DOI： 10.13422/j.cnki.syfjx.2017200090.

摘要

目的：以乌头汤为载体，研究加入半夏不同炮制品后对大鼠细胞色素P450酶系（CYP）3A1/2的影响，为阐述"十八反"中半夏反乌头的反性内涵提供实验依据。方法： CYP3A酶活性采用体外温孵法和体内探针法进行检测，酶蛋白和mRNA表达采用蛋白质免疫印迹法（Western blot）和荧光定量聚合酶链式反应技术进行检测。结果：与乌头汤加生半夏组相比，乌头汤加法半夏各剂量组6β-羟基睾酮（6β-OH-Tes）生成速率未发生显著性变化，CYP3A蛋白表达显著增加（P<0.01，P<0.05），CYP3A1 mRNA的表达仅在0.60 g · kg-1剂量组显著降低（P<0.01）；乌头汤加姜半夏在1.20 g · kg-1剂量组时6β-OH-Tes生成速率极显著降低（P<0.01），CYP3A蛋白表达仅在0.60 g · kg-1剂量组明显增加（P<0.05），CYP3A1 mRNA的表达在0.60，1.20 g · kg-1剂量组有显著降低（P<0.01）；在体内探针法试验中乌头汤加法/姜半夏组6'-羟基丁螺环酮（6'-OH-BP）和丁螺环酮（BP）的药时曲线下面积（AUC0-t）比值（6'-OH-BP/BP），1-（2-嘧啶基）哌嗪（1-PP）与BP的AUC0-t比值（1-PP/BP）均未发生明显变化。结论：不同半夏炮制品增强乌头汤对CYP3A的抑制作用的程度不同，这将会导致乌头汤中的双酯型生物碱类成分（如乌头碱）代谢减慢，从而引起药理作用的增强或毒性的增加。

Abstract

Objective: It was explored in the article that the compatibility connotation of Aconiti Radix and Pinelliae Rhizoma (PR) after the different processed products of PR was added to Wutoutang (WTT) from cytochrome P450 enzyme system (CYP) 3A1/2 medating metabolic herb-herbs interaction in rats. Method: The change of CYP3A enzymatic activity was detected by incubation in vitro and probe method in vivo.The expression of protein and mRNA was determined with Western blot and the fluorescence quantitative polymerase chain reaction (PCR) technology. Result: By comparing with WTT adding unprocessed Pinelliae Rhizoma (UPR)

the production rate of 6β-hydroxy-testosterone (6β-OH-Tes) did not change and the expression of CYP3A protein were increased (P<0.01

P<0.05) in WTT adding Pinelliae Rhizoma Praeparatum (PRP)

the mRNA expression of CYP3A1 was decreased (P<0.01) only in 0.60 g · kg-1 group of WTT adding PRP;the production rate of 6β-OH-Tes was very dramatically decreased (P<0.01) in 1.20 g · kg-1 group of WTT adding Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA)

the expression of CYP3A protein was increased (P<0.05) only in 0.60 g · kg-1 group of WTT adding PRPZA

the mRNA expression of CYP3A1 were markedly decreased (P<0.01) in 0.60

1.20 g · kg-1 groups of WTT adding PRPZA;the ratios between AUC0-t of 6'-hydroxy-buspirone (6'-OH-BP) and AUC0-t of buspirone (BP)

AUC0-t of 1-(2-pyrimidinyl)-piperazine (1-PP) and AUC0-t of BP did not change in WTT adding PRP/PRPZA by comparing with WTT adding UPR. Conclusion: Different processed products of PR can enhance the inhibition of WTT on CYP3A activity in various degree

which may slower the metabolism of diester diterpenoid alkaloids(such as aconitine) in WTT

and then lead to increase the toxicity or the pharmacological action of WTT.

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