To prescreen the in vivo neuroprotective activity of the chloroform, ethanol extracts of the leaves of Punicagranatum L.var. Ganesh family Punicaceae, commonly called pomegranate, using the model organism Aβ42 -amyloid neurotoxicity included Drosophila melanogaster. Chloroform(CEPGL), ethanol, (EEPGL) extracts were prepared, and its analysis by HPLC were carried out. Acute toxicity assessments were also performed. The neuroprotective effect of CEPGL, EEPGL in vivo was evaluated on the transgenic Aβ42 model of Drosophila melanogaster, a novel model system for screening drugs for Alzheimer’s disease by longevity assay, Climbing assay, Pseudopupil assay and nail polish imprint technique, and Scanning Electron Microscope (SEM). HPLC profile of the CEPGL, EEPGL showed the presence of Ursolic acid. Toxicity assessment using brine shrimp lethality bioassay (BSLA) of the CEPGL, EEPGL showed nontoxic up to 2500, 2000 ppm, respectively. The extracts possess potential in vivo neuroprotective activity on Drosophila melanogaster against beta-amyloid included neuronal toxicity. Conclusion: In the present study, we have presented the first evidence of the extracts of the leaves could significantly ameliorate the adverse morphological changes from Aβ42 protein in Drosophila, as indicated by prolonging the lifespan, by improving locomotor abilities and rescuing neuro-degeneration in ommatidia of Aβ42 expressing Drosophila which is comparable with donepezil. So it demonstrated the novel use of Ursolic acid of the extracts CEPGL, EEPGL effectively protect, rescue and most importantly, restore the impaired movement activity (i.e., climbing capability) in Drosophila melanogaster
