title: Neuroprotective effects of luteolin against apoptosis induced by 6-hydroxydopamine on rat pheochromocytoma PC12 cells.
abstract: BACKGROUND
  Apoptotic neuronal cell death plays an important role in Parkinson's disease (PD), a progressive neurodegenerative disorder. Luteolin, a flavonoid, has been shown to possess various pharmacological properties including strong antioxidant capacity.
  
  
  OBJECTIVE
  This study investigated the neuroprotective effect of luteolin against cytotoxicity induced by 6-hydroxy-dopamine (6-OHDA) (250 µM) in rat pheochromocytoma (PC12) cell line.
  
  
  METHODS
  The neuroprotective effect of luteolin against 6-OHDA-induced cytotoxicity in PC12 was evaluated by using cell viability test, nuclear staining and flow cytometry. In addition, the apoptotic role of luteolin was unveiled by monitoring mRNA expression of proapoptotic and anti-apoptotic genes.
  
  
  RESULTS
  Pretreatment with luteolin (3.13, 6.25, 12.5, 25 or 50 µM) could markedly attenuate 6-OHDA-induced PC12 cell viability loss in a concentration-dependent manner. Cell morphologic analysis and nuclear staining assays showed that luteolin (3.13, 12.5 or 50 µM) protected the cells from 6-OHDA-induced damage. As shown in the flow cytometry assay, the increased apoptotic rate induced by 6-OHDA could be significantly (p < 0.001) suppressed by luteolin (12.5 or 50 µM) pretreatment. The protection of luteolin (50 µM) against 6-OHDA-induced cell damage was shown to be through suppressing the over-expression of Bax gene (p < 0.01), inhibiting the reduction of Bcl-2 gene expression (p < 0.05) and markedly depressing the enhanced Bax/Bcl-2 ratio. Luteolin also downregulated the gene expression level of p53.
  
  
  CONCLUSIONS
  Luteolin has protective effects against 6-OHDA-induced cell apoptosis and might be a potential nutritional supplement which could be used to prevent neurodegenerative diseases such as PD.
authors.affiliation: State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, PR of China.
authors.forename: De-Jian
authors.initials: DJ
authors.lastname: Guo
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Peter Hoi-Fu
authors.initials: PH
authors.lastname: Yu
authors.forename: Shun-Wan
authors.initials: SW
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D047311:Luteolin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D016627:Oxidopamine; D047311:Luteolin