Calamintha incana (Sm.) Helder乙醇提取物对小鼠肝脏中药物代谢cyp450s mRNA表达的影响

Arwa R Althaher, Yazun Jarrar, Mahmood Ayad Al-Ibadah, Ruba Balasmeh, Qais Jarrar, Dina Abulebdah
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引用次数: 0

摘要

背景:药物代谢酶(DMEs)表达和活性的改变会改变药物的药代动力学,从而改变药物的反应。草药和水果中的一些化学物质会影响 DMEs 的表达。Calamintha incana 是中东阿拉伯国家常用的草药。目前还没有关于石菖蒲对肝脏 DMEs 表达影响的报告。目的:本研究旨在探讨服用石菖蒲对小鼠肝脏主要药物代谢细胞色素(cyp)P450 基因 mRNA 表达的影响:方法:采用液相色谱/质谱法分析乙酸提取物的化学成分。然后用 21 只 BALB/c 小鼠进行体内实验。小鼠被分为三组,每组七只。第一组(低剂量组)服用 41.6 毫克/千克的石菖蒲提取物,第二组服用高剂量(125 毫克/千克)的石菖蒲提取物,为期一个月。第三 "控制 "组的小鼠使用 20% 聚乙二醇 200 作为载体。然后,使用实时聚合酶链式反应分析cyp3a11、cyp2c29、cyp2d9和cyp1a1的表达。对小鼠肝脏相对重量和肝脏病理组织学改变进行了评估:结果:石菖蒲乙醇提取物中含有 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,低剂量的石菖蒲提取物能显著(P < 0.05)提高小鼠肝脏中 cyp3a11 的表达量,提高幅度超过 10 倍。此外,组织学分析表明,低剂量和高剂量服用石菖蒲提取物不会导致病理改变:从这些研究结果中可以得出结论,服用低剂量的白千层能上调小鼠 cyp3a11 的 mRNA 表达,但不会导致肝脏组织病理学改变。还需要进一步研究,以确定石菖蒲对由 cyp3a11 代谢的药物的药代动力学和反应的影响。
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Effects of Calamintha incana (Sm.) Helder Ethanolic Extract on the mRNA Expression of Drug-metabolizing cyp450s in the Mouse Livers.

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. Calamintha incana is commonly used in Middle Eastern Arabic countries. There is no report regarding the influence of Calamintha incana on the hepatic expression of DMEs.

Aims: The current investigation aimed to investigate the effect of Calamintha incana 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 Calamintha incana 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 Calamintha incana contained 27 phytochemical compounds. The most abundant compounds were linolenic acid, myristic acid, and p-cymene. It was found that the low dose of Calamintha incana 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 Calamintha incana on the pharmacokinetics and response of drugs metabolized by cyp3a11.

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