Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus.
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 (IC(50)) 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(50) = 0.3 μg/mL). It was also found that pyropheophorbide a possesses anti-HCV activity (IC(50) = 0.2 μg/mL). The 50%-cytotoxic concentrations (CC(50)) 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.
Division of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650 0017, Japan.
Suratno Lulut
SL
Ratnoglik
Chie
C
Aoki
Pratiwi
P
Sudarmono
Mari
M
Komoto
Lin
L
Deng
Ikuo
I
Shoji
Hiroyuki
H
Fuchino
Nobuo
N
Kawahara
Hak
H
Hotta
D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000821:virology; D006801:Humans; D032066:Morinda / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry
D000998:Antiviral Agents; D010936:Plant Extracts; D002734:Chlorophyll; C040298:pyropheophorbide a; C032623:pheophorbide a
antiviral; hepatitis C virus; pheophorbide a; pyropheophorbide a