METHODS: The effect of geraniin on DENV-2 RNA synthesis in infected Vero cells was tested using quantitative RT-PCR. The in vivo efficacy of geraniin in inhibiting DENV-2 infection was then tested using BALB/c mice with geraniin administered at three different times. The differences in spleen to body weight ratio, DENV-2 RNA load and liver damage between the three treatment groups as compared to DENV-2 infected mice without geraniin administration were determined on day eight post-infection.
RESULTS: Quantitative RT-PCR confirmed the decrease in viral RNA synthesis of infected Vero cells when treated with geraniin. Geraniin seemed to provide a protective effect on infected BALB/c mice liver when given at 24 h pre- and 24 h post-infection as liver damage was observed to be very mild even though a significant reduction of DENV-2 RNA load in serum was not observed in these two treatment groups. However, when administered at 72 h post-infection, severe liver damage in the form of necrosis and haemorrhage had prevailed despite a substantial reduction of DENV-2 RNA load in serum.
CONCLUSIONS: Geraniin was found to be effective in reducing DENV-2 RNA load when administered at 72 h post-infection while earlier administration could prevent severe liver damage caused by DENV-2 infection. These results provide evidence that geraniin is a potential candidate for the development of anti-dengue drug.
METHODS: Geraniin was prepared from Nephelium lappaceum rind by reverse phase C-18 column chromatography. Cytotoxicity of geraniin towards Vero cells was evaluated using MTT assay while IC50 value was determined by plaque reduction assay. The mode-of-action of geraniin was characterized using the virucidal, attachment, penetration and the time-of-addition assays'. Docking experiments with geraniin molecule and the DENV envelope (E) protein was also performed. Finally, recombinant E Domain III (rE-DIII) protein was produced to physiologically test the binding of geraniin to DENV-2 E-DIII protein, through ELISA competitive binding assay.
RESULTS: Cytotoxicity assay confirmed that geraniin was not toxic to Vero cells, even at the highest concentration tested. The compound exhibited DENV-2 plaque formation inhibition, with an IC50 of 1.75 μM. We further revealed that geraniin reduced viral infectivity and inhibited DENV-2 from attaching to the cells but had little effect on its penetration. Geraniin was observed to be most effective when added at the early stage of DENV-2 infection. Docking experiments showed that geraniin binds to DENV E protein, specifically at the DIII region, while the ELISA competitive binding assay confirmed geraniin's interaction with rE-DIII with high affinity.
CONCLUSIONS: Geraniin from the rind of Nephelium lappaceum has antiviral activity against DENV-2. It is postulated that the compound inhibits viral attachment by binding to the E-DIII protein and interferes with the initial cell-virus interaction. Our results demonstrate that geraniin has the potential to be developed into an effective antiviral treatment, particularly for early phase dengue viral infection.
METHODS: This is a follow-up study among 84 obese housewives without co-morbidities aged 18 to 59 years old who previously participated as a control group (delayed intervention, G1) in the My Body is Fit and Fabulous at Home (MyBFF@home) Phase II. Baseline data were obtained from 12 month data collection for this group. A new group of 42 obese housewives with co-morbidities (G2) were also recruited. Both groups received a 6 month intervention (July-December 2015) consisting of dietary counselling, physical activity (PA) and self-monitoring tools (PA diary, food diary and pedometer). Study parameters included weight, height, waist circumference, blood pressure and body compositions. Body compositions were measured using a bioelectrical impedance analysis device, Inbody 720. Descriptive and repeated measures ANOVA analyses were performed using SPSS 21.
RESULTS: There were reductions in mean body fat, fat mass and visceral fat area, particularly among obese women without co-morbidities. There were also decreases fat and skeletal muscle from baseline to month six with mean difference - 0.12 (95% CI: -0.38, 0.14) and visceral fat area from month three to month six with mean difference - 9.22 (- 17.87, - 0.56) for G1. G2 showed a decreasing pattern of skeletal muscle from baseline to month six with mean difference - 0.01(95% CI: -0.38, 0.37). There was a significant difference for group effect of visceral fat area (p