Effects of medicinal plant viscum album l. on rat liver flavin-containing monooxygenase activity and expression

Abstract

Viscum album L., a species of mistletoe, contains lectins, polypeptides, mucilage, sugar alcohols, flavonoids, lignans, triterpenes, and phenylallyl alcohols1. The leaves and twigs of Viscum album L., taken as tea, have been traditionally used for hypertension, stomachache, diarrhea, dysuria and also as analgesic and cardiotonic agent in Anatolia, Turkey2. In addition, in Europe, sterile extracts of Viscum album L. are among the most common herbal extracts applied in cancer treatment and have been used as prescription drugs, while in US, considered as dietary supplement3. Flavin-containing monooxygenases (FMOs, EC 1.14.13.8) are FAD-containing phase I enzymes and responsible for the oxidation of wide-range of nucleophilic nitrogen, sulfur, phosphorus, and selenium heteroatom-containing drugs such as tamoxifen, methimazole and imipramine, pesticides, neurotoxins, and other chemicals by using NADPH as cofactor4. The aim of this study was to determine the in vivo effects of Viscum album L. on FMO activity, mRNA and protein expression in rat liver. The water extract of Viscum album was injected intraperitonally (i.p) into 15 wistar albino rats as 10 mg/kg of body weight for 9 consecutive days, while 11 rats were used as control. Then, following the decapitation, the livers were removed and microsomal fractions were prepared. FMO activity using methimazole as substrate, mRNA expression by quantitative Real-Time PCR, and protein expression by Western Blot were determined. The results showed that extract of Viscum album L. decreased mRNA, and protein expressions as well as enzyme activity of FMO with respect to controls. Liver microsomal FMO activity was decreased from 5.1±0.9 to 4.1±1.1 nmol/min/mg (p<0.05). mRNA expression of FMO in extract injected animals was found to be 2.6 fold lower compared to controls (p<0.0001). In addition, the plant extract decreased the FMO protein level 28% with respect to controls (p<0.05). In conclusion, the metabolism of xenobiotics by FMO-catalyzed reactions may be altered due to the changes in FMO expression and activity by Viscum album L. extract.