IN VIVO ANTI-DENGUE STUDY OF SCHIZOPHYLLUM COMMUNE AQUEOUS EXTRACT IN AG129 MICE

Abstract

Intro: An effective antiviral therapies are currently unavailable for the treatment of DENV infection. Schizophyllum commune aqueous extract (ScASE) had been reported for the anti-dengue effect in in-vitro studies using plaque reduction assay and real time RT-PCR. This study explored the ability of this mushroom extract to give in vivo protection against dengue virus infection in the AG129 mouse model. Methods: Male AG129 mice at the age of 8 weeks were assigned into five groups of six: mock infected, DENV 2 infected, DENV 2 infected treated orally with ScASE (500 mg/kg), DENV 2 infected treated intraperitoneally with ScASE (500 mg/kg) and DENV2 infected treated intraperitoneally with celgosivir (15 mg/kg). The treatment doses were administered twice daily for 4 days. During the experiment, mice were weighed daily and their disease progression was visually monitored. At day 1, day 3, and day 5 post-infection, blood samples were collected for assessment of DENV titer by real time RT-PCR, NS1 Ag and inflammatory cytokine levels. Findings: After receiving intraperitoneal injections of 500 mg/kg of ScASE twice daily for four days, infected AG129 mice totally recovered from the disease and regained weight seven days after infection. The level of NS1 Ag significantly decreased to 80.12% while the quantity of viral RNA significantly reduced to 67.84%. On day 5 post-infection, strong anti-inflammatory effects were observed against the production of inflammatory cytokines, with percentage reductions of 45.8% for IL-6, 37.6% for IL-10, 78.3% for IL-12, 48.4% for MCP1, and 52.2% for TNF-α. Conclusion: This is a preliminary study that shown the potential of ScASE as an anti-dengue therapeutic drug in the AG129 mouse model. Before entering phase 1 clinical trial with human subjects, additional research must be carried out.