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

Suratno Lulut Ratnoglik, Chie Aoki, Pratiwi Pudjilestari Sudarmono, Mari Komoto, Lin Deng, Ikuo Shoji, Hiroyuki Fuchino, Nobuo Kawahara, Hak Hotta

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

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 6.6μg/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 =0.3μg/mL). It was also found that pyropheophorbide a possesses anti-HCV activity (IC50=0.2μg/mL). The 50%-cytotoxic concentrations (CC50) of pheophorbide a and pyropheophorbide a were 10.0 and 7.2μg/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.

Original languageEnglish
Pages (from-to)188-194
Number of pages7
JournalMicrobiology and Immunology
Volume58
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Antiviral
  • Hepatitis C virus
  • Pheophorbide a
  • Pyropheophorbide a

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