Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus

Authors

  • Suratno Lulut Ratnoglik,

    1. Division of Microbiology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
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  • Chie Aoki,

    1. Division of Microbiology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
    2. JST/JICA within the Science and Technology Research Partnership for Sustainable Development Laboratory, Tokyo, Japan
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  • Pratiwi Sudarmono,

    1. Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Tsukuba Ibaraki, Japan
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  • Mari Komoto,

    1. Division of Microbiology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
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  • Lin Deng,

    Corresponding author
    1. Division of Microbiology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
    • Correspondence

      Hak Hotta, Division of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650 0017, Japan. Tel:+81 78 382 5500; fax: +81 78 382 5519; e-mail: hotta@kobe-u.ac.jp

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  • Ikuo Shoji,

    1. Division of Microbiology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
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  • Hiroyuki Fuchino,

  • Nobuo Kawahara,

  • Hak Hotta

    1. Division of Microbiology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
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Abstract

The development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still needed. Antiviral compounds in medicinal plants are potentially good targets to study. Morinda citrifolia is a common plant distributed widely in Indo-Pacific region; its fruits and leaves are food sources and are also used as a treatment in traditional medicine. In this study, using a HCV cell culture system, it was demonstrated that a methanol extract, its n-hexane, and ethyl acetate fractions from M. citrifolia leaves possess anti-HCV activities with 50%-inhibitory concentrations (IC50) of 20.6, 6.1, and 6.6 μg/mL, respectively. Bioactivity-guided purification and structural analysis led to isolation and identification of pheophorbide a, the major catabolite of chlorophyll a, as an anti-HCV compound present in the extracts (IC50  = 0.3 μg/mL). It was also found that pyropheophorbide a possesses anti-HCV activity (IC50 = 0.2 μg/mL). The 50%-cytotoxic concentrations (CC50) of pheophorbide a and pyropheophorbide a were 10.0 and 7.2 μg/mL, respectively, their selectivity indexes being 33 and 36, respectively. On the other hand, chlorophyll a, sodium copper chlorophyllin, and pheophytin a barely, or only marginally, exhibited anti-HCV activities. Time-of-addition analysis revealed that pheophorbide a and pyropheophorbide a act at both entry and the post-entry steps. The present results suggest that pheophorbide a and its related compounds would be good candidates for seed compounds for developing antivirals against HCV.

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