Nur Hana Md Jelas

Background: Dengue is a vector-borne disease caused by four serotypes of dengue virus (DENV), spread rapidly through Aedes mosquito bites in tropical and subtropical regions. Due to the unavailability of approved antiviral treatment for dengue, continued effort to discover antiviral candidates from natural resources is in need. Purpose: In this study, Syzygium myrtifolium (stems) and Syzygium grande (leaves and stems) extracts were assessed for their cytotoxicity and antiviral activity against DENV2 in vitro. Methods: The antiviral properties of methanolic extracts of S. myrtifolium (stem) and S. grande (leaves and stem) were determined by exposing the serially diluted extracts on DENV2-infected African green monkey kidney (Vero) and human hepatocellular carcinoma (Huh-7). The infection rate was measured by an immunofluorescence-based high-content screening technique. The synthesis of virus progeny was measured by a plaque assay. The ATP-based luminescent assay was used to determine the cytotoxicity effect of the extracts on Vero cells and Huh-7. Results: Low cytotoxicity effects of S. myrtifolium (stem) and S. grande (leaves and stem) extracts were shown in Huh-7 and Vero cells with CC₅₀ ranges from >133 to 67.36 μg/mL. The extracts of S. myrtifolium stems, S. grande leaves and S. grande stems showed potent antiviral activities at the pre-infection phase in Vero cells with EC₅₀ of 5.57, 5.37 and 10.13 μg/mL, respectively. At the post-infection phase, S. myrtifolium stem and S. grande leaf and stem extract treatments also resulted in infection-inhibitory effects with EC₅₀ of 15.01, 13.45 and 10.33 μg/mL, respectively. However, reduced antiviral activities of the extracts were observed in Huh-7 cells with EC₅₀ ranges from 40.23 to 82.83 μg/mL. Conclusions: This study provides scientific evidence on Syzygium myrtifolium and Syzygium grande as promising candidates for further investigation in the development of dengue antivirals.

The role of Carica papaya L. leaf juice in immune dysregulation caused by dengue virus infection remains unclear. This study aimed to investigate the immunomodulatory activities of the freeze-dried C. papaya leaf juice (FCPLJ) on AG129 mice infected with a clinical DENV-2 (DMOF015) isolate. The infected AG129 mice were orally treated with 500 and 1000 mg/kg/day of FCPLJ, for three days. Platelet, leukocyte, lymphocyte and neutrophil counts were microscopically determined. The level of plasma proinflammatory cytokines was measured by multiplex immunoassay. The levels of intracellular cytokines and viral RNA were determined by RT-qPCR technique. The results showed that the FCPLJ treatment increased the total white blood cell and neutrophil counts in the infected mice. The FCPLJ treatment decreased the level of GM-CSF, GRO-alpha, IL-1 beta, IL-6, MCP-1 and MIP-1 beta in the plasma of the infected mice. The intracellular IL-6 and viral RNA levels in the liver of infected mice were decreased by the FCPLJ treatment. In conclusion, this study supports the potential immunomodulatory role of the FCPLJ in a non-lethal, symptomatic dengue mouse model. Further studies on the action mechanism of the C. papaya leaf juice and its possible use as adjunctive dengue immunotherapy are warranted.