Cytoprotective effects of hesperetin and hesperidin against amyloid ß-induced impairment of glucose transport through downregulation of neuronal autophagy

Scope: This study investigated whether flavonoids, such as hesperetin and hesperidin, inhibited amyloid beta (A beta)-impaired glucose utilization through regulating cellular autophagy in insulin-stimulated neuronal cells. Methods and results: In this study, we used a toxic A beta 1-42 peptide to impair insulin-stimulated glucose utilization in Neuro-2A cells, and this study also hypothesized that A beta-induced autophagy might be emerging as a key process regulating neuronal glucose uptake. Additionally, hesperetin and hesperidin were used to test the neuroprotective effect against A beta-induced impairment of glucose utilization. Our data found that A beta-stimulated autophagy activation promoted the phenomenon of impairment of neuronal energy metabolism, including glucose uptake, glucose transporters (GLUTs), and insulin signaling cascades. In this study, confocal images of autophagy punctate further confirmed that downregulation of A beta-stimulated autophagy could increase insulin-stimulated neuronal glucose uptake. Moreover, treatment with hesperetin and hesperidin improved A beta-impaired glucose utilization by inhibiting A beta-induced autophagy in neuronal cells. Conclusion: These findings suggest that downregulation of autophagy may be one of the approaches to control the impairment of energy metabolism leading to neuronal injury in the early development of Alzheimer's disease, and hesperetin or hesperidin may be a potential agent in the preventing of Alzheimer's disease progression.