title: Cytoprotective effects of hesperetin and hesperidin against amyloid β-induced impairment of glucose transport through downregulation of neuronal autophagy.
abstract: METHODS
  This study investigated whether flavonoids, such as hesperetin and hesperidin, inhibited amyloid β (Aβ)-impaired glucose utilization through regulating cellular autophagy in insulin-stimulated neuronal cells.
  
  
  RESULTS
  In this study, we used a toxic Aβ1-42 peptide to impair insulin-stimulated glucose utilization in Neuro-2A cells, and this study also hypothesized that Aβ-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 Aβ-induced impairment of glucose utilization. Our data found that Aβ-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 Aβ-stimulated autophagy could increase insulin-stimulated neuronal glucose uptake. Moreover, treatment with hesperetin and hesperidin improved Aβ-impaired glucose utilization by inhibiting Aβ-induced autophagy in neuronal cells.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Shang-Ming
authors.initials: SM
authors.lastname: Huang
authors.forename: Shin-Yi
authors.initials: SY
authors.lastname: Tsai
authors.forename: Jer-An
authors.initials: JA
authors.lastname: Lin
authors.forename: Chi-Hao
authors.initials: CH
authors.lastname: Wu
authors.forename: Gow-Chin
authors.initials: GC
authors.lastname: Yen
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection; D015536:Down-Regulation; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; C495689:Slc2a3 protein, mouse; C495693:Slc2a4 protein, mouse; C075222:amyloid beta-protein (1-42); D006569:Hesperidin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; C013015:hesperetin