title: Ethanolic Extract of Melia Fructus Has Anti-influenza A Virus Activity by Affecting Viral Entry and Viral RNA Polymerase.
abstract: Meliae Fructus (MF) is the dried ripe fruit ofMelia toosendanSiebold et Zuccarini, Meliaceae family. MF is widely used in traditional medicine to treat inflammation and helminthic infection and has anti-bacterial, anti-oxidant, anti-cancer, anti-inflammatory, and analgesic activities. However, potential anti-influenza properties of MF have yet to be investigated. We determined whether an ethanolic extract of MF (EMF) has anti-viral activity via an EMF pre-, co-, and post-treatment assay, using the Influenza A/PR/8/34 and H3N2 virus on Madin-Darby canine kidney (MDCK) cells. The EMF had anti-influenza virus activity in pre- and co-treated cells in a dose-dependent manner, but not in post-treated cell. EMF inhibited the activity of hemagglutinin (HA) and neuraminidase (NA) of influenza virus. EMF inhibited viral HA, nucleoprotein (NP), matrix protein 2 (M2), non-structural protein 1 (NS1), polymerase acidic protein (PA), polymerase basic protein 1 (PB1), and polymerase basic protein 2 (PB2) mRNA synthesis at 5 h post infection (hpi), however, the levels of PA, PB1, and PB2 mRNA were increased in pre- and co-EMF treated cells compared with control virus-infected and EMF post-treated cells at 18 hpi. The level of M2 protein expression was also decreased upon pre- and co-treatment with EMF. The PA protein was accumulated and localized in not only the nucleus but also the cytoplasm of virus-infected MDCK cells at 18 hpi. Pre-EMF treatment inhibited the expression of pAKT, which is induced by influenza virus infection, at the stage of virus entry. We also found that treatment of EMF up-regulated the antiviral protein Mx1, which may play a partial role in inhibiting influenza virus infection in pre- and co-EMF treated MDCK cells. In summary, these results strongly suggested that an ethanolic extract of Meliae Fructus inhibited influenza A virus infection by affecting viral entry, PA proteins of the RNA polymerase complex, and Mx1 induction and may be a potential and novel anti-influenza agent.
authors.affiliation: Korean Medicine Application Center, Korea Institute of Oriental Medicine Daegu, South Korea.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Jin
authors.affiliation: Korean Medicine Application Center, Korea Institute of Oriental Medicine Daegu, South Korea.
authors.forename: Jang-Gi
authors.initials: JG
authors.lastname: Choi
authors.affiliation: Korean Medicine Application Center, Korea Institute of Oriental Medicine Daegu, South Korea.
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
authors.affiliation: Korean Medicine Application Center, Korea Institute of Oriental Medicine Daegu, South Korea.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
keywords: A/PR/8/34; H3N2; MDCK; Meliae Fructus; PA; influenza virus; viral entry