Therapeutic potential of luteolin in transgenic Drosophila model of Alzheimer's disease

Abstract

A transgenic fly line expressing wild type human Aβ42 were exposed to luteolin mixed in diet at final concentration of 5, 10, 15 and 20μM. The climbing assay, activity pattern, life span, aversive phototaxis suppression assay (APS) along with the estimation of protein carbonyl content (PCC), glutathione-S-transferase (GSTs) activity, glutathione (GSH) content, lipid peroxidation (LPO), acetylcholinesterase activity (AChE), superoxide dismutase (SOD) activity, catalase (CAT) activity, caspase 3 and 9 activities in the brain of treated as well as untreated AD flies (Positive control) were studied. Histopathology of Drosophila brain sections was done by performing thioflavin-S, Bielschowsky's silver staining and toluidine blue staining. A dose-dependent increase in the life span, delay in the loss of climbing ability as well as activity was observed in AD flies exposed to luteolin compared to unexposed AD flies. A dose-dependent reduction in LPO, PCC, GST, AChE, SOD, CAT, caspase 9 and caspase 3 activity and an increase in the GSH content was also observed. Histopathological examination of fly brains using thioflavin-S and silver staining has revealed a significant dose-dependent reduction in the expression of Aβ42 peptides in AD fly groups exposed to 10, 15 and 20μM of luteolin. No gross morphological changes were observed in the brain sections of AD and control flies stained with toluidine blue. Molecular docking results have revealed that luteolin binds to AChE and Aβ42 at specific sites that might result in the inhibition of AChE and disaggregation/prevention of Aβ42 plaque formation.

Keywords: Alzheimer’s disease; Luteolin; Neurodegeneration; Oxidative stress.