title: The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels.
abstract: Despite recent progress in the development of direct-acting antivirals against hepatitis C virus (HCV), chronic HCV infection remains an important health burden worldwide. MicroRNA122 (miR122), a liver-specific microRNA (miRNA), positively regulates HCV replication, and systemic application of antisense oligonucleotides against miR122 led to the long-lasting suppression of HCV viremia in human clinical trials. Here, we report that apigenin, a flavonoid and an inhibitor of maturation of a subset of miRNAs, inhibits HCV replication in vitro. Apigenin decreased the expression levels of mature miR122 without significantly affecting cell growth. Because supplementation of synthesized miR122 oligonucleotides or overexpression of constitutively active TRBP blocked these effects, the inhibitory effects of apigenin on HCV replication seemed to be dependent on the reduction of mature miR122 expression levels through inhibition of TRBP phosphorylation. Thus, apigenin intake, either through regular diet or supplements, may decrease HCV replication in chronically infected patients.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 5-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Shibata
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 5-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Ohno
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 5-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Japan Science and Technology Agency, PRESTO, Kawaguchi-shi, Saitama 332-0012, Japan. Electronic address: otsukamo-tky@umin.ac.jp.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 5-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kishikawa
authors.affiliation: Unit of Disease Control Genome Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Kaku
authors.initials: K
authors.lastname: Goto
authors.affiliation: Unit of Disease Control Genome Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Muroyama
authors.affiliation: Unit of Disease Control Genome Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 5-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 5-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Takata
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 5-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D047310:Apigenin / Q000378:metabolism*; D002460:Cell Line; D016174:Hepacivirus / Q000187:drug effects*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D047310:Apigenin
keywords: HCV; MicroRNA; Polyphenol; Replicon