Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus. (March 2014)

• Record Type: Journal Article
• Authors: Ratnoglik, Suratno Lulut; Aoki, Chie; Sudarmono, Pratiwi; Komoto, Mari; Deng, Lin; Shoji, Ikuo; Fuchino, Hiroyuki; Kawahara, Nobuo; Hotta, Hak
• Is Part Of: Microbiology and immunology. Volume 58:Number 3(2014:Mar.)
• Page Start: 188
• Page End: 194
• Publication Date: 2014-03
• Subjects: Microbiology -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Microbiology -- Periodicals; Microbiologie -- Périodiques; Immunologie -- Périodiques; 579
• DOI: 10.1111/1348-0421.12133
• Languages: English
• ISSNs: 0385-5600

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="mim12133-sec-0001" sec-type="section"> <p>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. <italic>Morinda citrifolia</italic> 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 <italic>n</italic>‐hexane, and ethyl acetate fractions from <italic>M. citrifolia</italic> leaves possess anti‐HCV activities with 50%‐inhibitory concentrations (IC<sub>50</sub>) 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 (IC<sub>50</sub> = 0.3 μg/mL). It was also found that pyropheophorbide a possesses anti‐HCV activity (IC<sub>50</sub> = 0.2 μg/mL). The 50%‐cytotoxic concentrations (CC<sub>50</sub>) 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.</p> </sec> </abstract>