Phytochemicals exert antiviral activity and may play a potential therapeutic role in hepatitis C virus (HCV) infection. In this work, we aimed to isolate NS3 inhibitors from traditional Indian medicinal plants that were found, in our earlier study, to inhibit HCV NS3 protease activity and to evaluate their potential to inhibit HCV replication. A potent inhibitory effect of NS3 catalytic activity was obtained with Embelia ribes plant extracts. Quercetin, a ubiquitous plant flavonoid, was identified as the active substance in the fractioned extract. It was found to inhibit NS3 activity in a specific dose-dependent manner in an in vitro catalysis assay. Quercetin inhibited HCV RNA replication as analysed in the subgenomic HCV RNA replicon system. It also inhibited HCV infectious virus production in the HCV infectious cell culture system (HCVcc), as analysed by the focus-forming unit reduction assay and HCV RNA real-time PCR. The inhibitory effect of quercetin was also obtained when using a model system in which NS3 engineered substrates were introduced in NS3-expressing cells, providing evidence that inhibition in vivo could be directed to the NS3 and do not involve other HCV proteins. Our work demonstrates that quercetin has a direct inhibitory effect on the HCV NS3 protease. These results point to the potential of quercetin as a natural nontoxic anti-HCV agent reducing viral production by inhibiting both NS3 and heat shock proteins essential for HCV replication.

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In this study, twenty-eight South Indian medicinal plants were screened for their anti-fungal activity against six species of fungi (Trichophyton mentagrophytes, T. rubrum, T. soudanense, Candida albicans, Torulopsis glabrata, and C. krusei). Three plant species extracts, Celastrus paniculatus, Eriodendron anfractuosum and Ficus glomerata showed inhibitory activity. An aqueous extract of galls of Terminalia chebula showed inhibitory effects on three dermatophytes (Trichophyton spp.) and three yeasts (Candida spp.). Seeds extract of T. chebula inhibited only the growth of T. glabrata. An aqueous extract of T. chebula showed inhibitory effects higher than those measured in ethanol extracts. It is therefore suggested that tannins are plausible candidates for the anti-dermatophytic effects of T. chebula. Chebulinic acid, a known tannin of T. chebula was tested and found not inhibitory, thus a search for the active compound is needed.

Aqueous plant extracts of 63 desert plants collected in the Negev desert and Bedouin market (Beer Sheva) were screened for larvicidal activity. Larvicidal activity was found in 16 plants, of which seven were reported in the ethnobotanical literature to be either poisonous, vermifuge, abortive, or toxic. Seven species showed high toxicity against Aedes aegypti larvae: Ephedra aphylla, Gypsophila arabica, Anabasis articulata, Mesembryanthemum nodiflorum, Nicotiana rustica, Hammada scoparia, Achillea fragrantissima. Four species showed moderate toxicity: Foeniculum vulgare, Glaucium arabicum, Solanum elaeagnifolium and Peganum harmala. The species with the lowest LC 50 values are: Ephedra aphylla, Gypsophila arabica and Achillea fragrantissima and may be candidates for further isolation and characterization of larvicidal compounds, which could be important in controlling disease-causing mosquitoes. Cytotoxicity of aqueous extract of Gypsophila arabica on melanoma cells in vitro showed that screening for larvicidal compounds may be used as a preliminary screening step in the search of anti-cancerous compounds.

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