title: Digitoflavone provokes mitochondrial biogenesis in PC12 cells: A protective approach to oxidative stress.
abstract: BACKGROUND
  Reactive oxygen species (ROS) are known to be one of the main causes of neurodegenerative disorders, and flavonoids play characteristic roles in a variety of biological activities, and specially are known to be antioxidant reagents.
  
  
  OBJECTIVE
  In this study, we investigated neuroprotective effects of digitoflavone to suppress H2O2 -induced cell death in neuron-like PC12 cells.
  
  
  METHODS
  PC12 cells were pre-treated with digitoflavone for 2 h and then cells were exposed to H2O2 for 18 h. The cells' viability was evaluated by MTT assay. Rhodamine 123 staining was used for the determination of mitochondrial membrane potential (ΔΨm). The intracellular ROS aggregation was determined by using 2',7'-dichlorofluorescein diacetate. Also, the level of mitochondrial biogenesis factors was measured by western blot. The antioxidant capacity of digitoflavone was also determined by measuring reduced glutathione (GSH) level and catalase (CAT) activity quantification.
  
  
  RESULTS
  Digitoflavone significantly elevated cells' viability at concentrations of 10 and 20 µM. Also, digitoflavone attenuated intracellular level of ROS, and stabilized ΔΨm. Moreover, digitoflavone increased phosphorylation of AMP-activated protein kinase (AMPK) and, consequently, elevated mitochondrial biogenesis factors which were reduced after H2O2 exposure. We emphasized on the protective effect of digitoflavone through increasing mitochondrial biogenesis by specifically inhibiting AMPK. Antioxidant ability of digitoflavone was indicated by the elevation of GSH level and CAT activity.
  
  
  CONCLUSIONS
  As a result, digitoflavone stabilize ΔΨm, enhanced cell viability through inducing mitochondrial biogenesis pathway, and increased antioxidant capacity of the cells which lead to better combating the oxidative stress.
authors: NeuroBiology Research Center and.
authors: Asal
authors: A
authors: Yans
authors: Shima Zareh
authors: SZ
authors: Shahamati
authors: Amir Hossein
authors: AH
authors: Maghsoudi
authors: Nader
authors: N
authors: Maghsoudi
mesh_terms: D000818:Animals; D002470:Cell Survival; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D001678:Organelle Biogenesis; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047309:Flavones; D017382:Reactive Oxygen Species
keywords: Antioxidant; flavonoids; mitochondrial membrane potential; neuroprotection; reactive oxygen species