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

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 (IC 50 ) of 20.6, 6.1, and 6.6 mg/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 ¼ 0.3 mg/mL). It was also found that pyropheophorbide a possesses anti-HCV activity (IC 50 ¼ 0.2 mg/mL). The 50%-cytotoxic concentrations (CC 50 ) of pheophorbide a and pyropheophorbide a were 10.0 and 7.2 mg/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.

Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Ruta angustifolia leaves

“…We tested ethanol extracts of Indonesia plants for their anti-HCV activities and reported that Toona sureni leaves, Melicope latifolia leaves, Melanolepis multiglandulosa stem and Ficus fistulosa leaves possessed anti-HCV activities [10]. We also reported that extracts of Glycyrrhiza uralensis root and isolated compounds, such as glycycoumarin, glycerin, glycyrol, and liquiritigenin, and extracts of Morinda citrifolia leaves, an isolated compound, pheophorbide a, and its related compound, pyropheophorbide a, exhibited anti-HCV activities [11,12]. Likewise, silymarin, iridoid, epigallocatechin-3-gallate were reported to inhibit HCV infection at the entry step while diosgenin, luteolin, quercetin, 3-hydroxy caruilignan C, excoecariphenol D and apigenin at the post-entry step [13,14].…”

Advance in studies on traditional Chinese medicines to treat infection with the hepatitis B virus and hepatitis C virus

“…In addition to inhibiting HCV entry, compounds also inhibit viral infection after entry. Ratnoglik et al found that pheophorbide A and pyropheophorbide, two active compounds isolated from Morinda citrifolia, inhibited HCV infection by interrupting viral RNA replication and viral protein production (63). Silybin B, a silymarin isolated from Silybum marianum, inhibited HCV infection in 2 ways (64).…”

Antihepatitis C Virus Activity of Indonesian Mahogany (Toona Sureni)

“…A major catabolite of chlorophyll A, which was isolated from Morinda citrifolia and identified as pheophorbide A, was reported to possess anti-HCV activity with IC 50 value of 0.3 µg/ml. It was reported also that pyropheophorbide A is an anti-HCV compound with IC 50 value of 0.2 µg/ml [10]. Adianti et al suggested that glycycoumarin, glycerin, glycerol, and liquiritigenin isolated from Glycyrrhiza uralensis, as well as isoliquiritigenin, licochalcone A, and glabridin, would be good candidates for seed compounds to develop antivirals against HCV [11].…”