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

Abstract

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. The current investigation aimed to investigate the effect of Calamintha incana consump-tion on the mRNA expression of major hepatic drug-metabolizing cytochrome (cyp) P450 genes in mice. The chemical composition of the ethanoic extract was analyzed using liquid chroma-tography/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 "con-trol" 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 reac-tion. The relative liver weights of the mice and the hepatic pathohistological alterations were assessed. 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 expres-sion 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 patholog-ical alterations. It can be concluded from these findings that consumption of low doses of Cala-mintha incana upregulated the mRNA expression of mouse cyp3a11 without causing histopatho-logical alterations in the livers. Further studies are needed to determine the influence of Cala-mintha incana on the pharmacokinetics and response of drugs metabolized by cyp3a11.