title: Induction of Flavin-Containing Monooxygenase in Mice by Oral Administration of Phellinus baumii (Agaricomycetes) Extract.
abstract: Phellinus baumii is a yellow mushroom long used in alternative medicine in Korea and other central Asian countries. To identify genes affected by a single or 7-day oral administration of a water extract of Ph. Baumii, mouse liver tissue was analyzed using microarrays. The results showed that 8 and 23 genes were upregulated and 3 and 11 genes downregulated more than 3-fold by single and multiple oral administrations of 100 mg/kg PBE, respectively. Among the upregulated genes, the expression of 3 flavin-containing monooxygenase (Fmo) family genes, Fmo2-4, was upregulated in a concentration-dependent manner. The microarray analysis also showed that single and multiple administrations of PBE increased Fmo3 expression in the mouse liver by 5.1- and 17.6-fold, respectively. To validate the Fmo expression microarray data, polymerase chain reaction was used to confirm the induction of Fmo subclass genes. Mice were orally administered Ph. Baumii extract (PBE), Ph. Baumii water, or Ph. Baumii β-glucan fraction (PBG) for 7 days, and induction of the expression of the Fmo subclasses in the liver, lung, and kidney was investigated. Fmo2, Fmo3, and Fmo4 expression was induced by both PBE and PBG in the lung, liver, and kidney, respectively. However, no induction of Fmo1 and Fmo5 was detected. To investigate the metabolic acceleration of xenobiotic by PBE, carbendazim was orally administered to mice and its clearance from the blood analyzed. High-performance liquid chromatography analysis showed accelerated clearance of serum carbendazim by oral administration of PBE for 7 days, as evidenced by the reduced peak plasma concentration, time to reach the peak plasma concentration, and area under the curve values. Moreover, PBE increased the carbendazim clearance rate at the higher concentration. These data indicate that oral administration of PBE resulted in modulation of gene expression: PBE was responsible for the induction of Fmo2, Fmo3, and Fmo4 expression. PBE also accelerated the metabolic clearance of carbendazim in vivo and so could be applied to the detoxification of xenobiotics such as drugs, pesticides, and nicotine.
authors.affiliation: Department of Life Science, University of Seoul, Seoul, Korea.
authors.forename: Batbayar
authors.initials: B
authors.lastname: Sainkhuu
authors.affiliation: Department of Life Science, University of Seoul, Seoul, Korea.
authors.forename: Beom Su
authors.initials: BS
authors.lastname: Park
authors.affiliation: College of Pharmacy, and Department of Life Science, University of Seoul, Korea.
authors.forename: Ha Won
authors.initials: HW
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D000969:Antinematodal Agents / Q000378:metabolism / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000378:metabolism / Q000493:pharmacokinetics; D002219:Carbamates / Q000378:metabolism / Q000493:pharmacokinetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D040081:Protein Array Analysis; D015203:Reproducibility of Results
chemical_list: D000969:Antinematodal Agents; D001562:Benzimidazoles; D002219:Carbamates; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); C006698:carbendazim