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(Sm.)Helder 乙醇提取物对小鼠肝脏中药物代谢酶 CYP450s mRNA 表达的影响。

Effects of (Sm.) Helder Ethanolic Extract on the mRNA Expression of Drug-metabolizing cyp450s in the Mouse Livers.

机构信息

Department of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.

Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, 19117, Jordan.

出版信息

Microrna. 2024;13(1):63-70. doi: 10.2174/0122115366268781231205103752.

DOI:10.2174/0122115366268781231205103752
PMID:38265404
Abstract

BACKGROUND

Alteration in the expression and activity of drug-metabolizing enzymes (DMEs) can alter the pharmacokinetics and hence the response of the drug. Some chemicals found in herbs and fruits affect the expression of DMEs. is commonly used in Middle Eastern Arabic countries. There is no report regarding the influence of on the hepatic expression of DMEs.

AIMS

The current investigation aimed to investigate the effect of consumption on the mRNA expression of major hepatic drug-metabolizing cytochrome (cyp) P450 genes in mice.

METHODS

The chemical composition of the ethanoic extract was analyzed using liquid chromatography/ mass spectrometry. Then, 21 BALB/c mice were used for the in vivo experiment. The mice were divided into three groups, each consisting of seven mice. The first group (low-dose group) was treated with 41.6 mg/kg of extract and the second group was administered the high-dose (125 mg/kg) of the extract for one month. The mice in the third "control" group administrated the vehicle 20% polyethylene glycol 200. Then, the expression of cyp3a11, cyp2c29, cyp2d9, and cyp1a1 was analyzed using the real-time polymerase chain reaction. The relative liver weights of the mice and the hepatic pathohistological alterations were assessed.

RESULTS

The ethanolic extract of contained 27 phytochemical compounds. The most abundant compounds were linolenic acid, myristic acid, and p-cymene. It was found that the low dose of extract upregulated significantly (P < 0.05) the expression of cyp3a11 by more than ten folds in the liver of treated mice. Furthermore, the histological analysis showed that low- and high-dose administration of the C. incana did not cause pathological alterations.

CONCLUSION

It can be concluded from these findings that consumption of low doses of Calamintha incana upregulated the mRNA expression of mouse cyp3a11 without causing histopathological alterations in the livers. Further studies are needed to determine the influence of on the pharmacokinetics and response of drugs metabolized by cyp3a11.

摘要

背景

药物代谢酶(DME)的表达和活性的改变会改变药物的药代动力学,从而影响药物的反应。一些草药和水果中的化学物质会影响 DME 的表达。 在中东阿拉伯国家被广泛使用。目前还没有关于 对肝内 DME 表达影响的报告。

目的

本研究旨在探讨 摄入对小鼠主要肝药物代谢细胞色素(cyp)P450 基因 mRNA 表达的影响。

方法

采用液相色谱/质谱法分析醇提物的化学成分。然后,将 21 只 BALB/c 小鼠用于体内实验。将小鼠分为三组,每组 7 只。第一组(低剂量组)给予 41.6mg/kg 的 提取物,第二组给予 125mg/kg 的高剂量提取物,为期一个月。第三组“对照组”给予 20%聚乙二醇 200 作为载体。然后,采用实时聚合酶链反应分析 cyp3a11、cyp2c29、cyp2d9 和 cyp1a1 的表达。评估小鼠的相对肝重和肝组织病理学改变。

结果

的乙醇提取物含有 27 种植物化学物质。最丰富的化合物是亚麻酸、肉豆蔻酸和对伞花烃。研究发现,低剂量的 提取物显著上调(P <0.05)了处理小鼠肝脏中 cyp3a11 的表达,上调幅度超过 10 倍。此外,组织学分析表明,低剂量和高剂量的 C. incana 给药不会引起病理改变。

结论

从这些发现可以得出结论,低剂量的 Calamintha incana 摄入可上调小鼠 cyp3a11 的 mRNA 表达,而不会引起肝脏的组织病理学改变。需要进一步研究确定 对 cyp3a11 代谢药物的药代动力学和反应的影响。

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