title: Protective effect of Bu-7, a flavonoid extracted from Clausena lansium, against rotenone injury in PC12 cells.
abstract: OBJECTIVE
  To investigate the protective effect and underlying mechanisms of Bu-7, a flavonoid isolated from the leaves of Clausena lansium, against rotenone-induced injury in PC12 cells.
  
  
  METHODS
  The cell viability was evaluated using MTT assay. The cell apoptosis rate was analyzed using flow cytometry. JC-1 staining was used to detect the mitochondrial membrane potential (MMP). Western blotting analysis was used to determine the phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), tumor protein 53 (p53), Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and caspase 3.
  
  
  RESULTS
  Treatment of PC12 cells with rotenone (1-20 μmol/L) significantly reduced the cell viability in a concentration-dependent manner. Pretreatment with Bu-7 (0.1 and 10 μmol/L) prevented PC12 cells from rotenone injury, whereas Bu-7 (1 μmol/L) had no significant effect. Pretreatment with Bu-7 (0.1 and 10 μmol/L) decreased rotenone-induced apoptosis, attenuated rotenone-induced mitochondrial potential reduction and suppressed rotenone-induced protein phosphorylation and expression, whereas Bu-7 (1 μmol/L) did not cause similar effects. Bu-7 showed inverted bell-shaped dose-response relationship in all the effects.
  
  
  CONCLUSIONS
  Bu-7 protects PC12 cells against rotenone injury, which may be attributed to MAP kinase cascade (JNK and p38) signaling pathway. Thus, Bu-7 may be a potential bioactive compound for the treatment of Parkinson's disease.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bo-yu
authors.initials: BY
authors.lastname: Li
authors.forename: Yu-he
authors.initials: YH
authors.lastname: Yuan
authors.forename: Jin-feng
authors.initials: JF
authors.lastname: Hu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.forename: Dong-ming
authors.initials: DM
authors.lastname: Zhang
authors.forename: Nai-hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054700:Clausena / Q000737:chemistry*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D007306:Insecticides / Q000009:adverse effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D012402:Rotenone / Q000009:adverse effects*
chemical_list: D005419:Flavonoids; D007306:Insecticides; D010936:Plant Extracts; D012402:Rotenone