Methods: Antioxidant properties were assessed through various radical (DPPH, ABTS, and nitric oxide) scavenging assays and determination of total phenolic content and ferric reducing antioxidant power level. ARPE-19 cells were preincubated with samples before the addition of GO (to generate H2O2). Cell viability, change in intracellular reactive oxygen species (ROS), H2O2 levels in cell culture supernatant, and gene expression were assessed.
Results: F2 showed higher antioxidant levels than the extract when assessed for radical scavenging activities and ferric reducing antioxidant power. F2 protected the ARPE-19 cells against GO-H2O2-induced oxidative stress by reducing the production of H2O2 and intracellular reactive oxygen species. This was achieved by the activation of nuclear factor erythroid 2-related factor 2 (Nrf2/NFE2L2) and superoxide dismutase (SOD2), as well as downregulation of nitric oxide producer (NOS2) at the transcriptional level.
Conclusions: The results showed that myricetin derivatives from S. malaccense have the capacity to exert considerable exogenous antioxidant activities and stimulate endogenous antioxidant activities. Therefore, these derivatives have excellent potential to be developed as therapeutic agents for managing DR.
OBJECTIVE: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease.
METHODOLOGY: Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.
RESULTS: In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC50 was predicted as 6.025 nM.
CONCLUSION: Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.