Bo-yu Li1, Yu-he Yuan, Jin-feng Hu, Qing Zhao, Dong-ming Zhang, Nai-hong Chen. 1. 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.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: 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. CONCLUSION: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: N Vanacore; A Nappo; M Gentile; A Brustolin; S Palange; A Liberati; S Di Rezze; G Caldora; M Gasparini; F Benedetti; V Bonifati; F Forastiere; A Quercia; G Meco Journal: Neurol Sci Date: 2002-09 Impact factor: 3.307
Authors: Javier Cifuentes; Vivian A Salazar; Mónica Cuellar; María Claudia Castellanos; Jader Rodríguez; Juan C Cruz; Carolina Muñoz-Camargo Journal: Antioxidants (Basel) Date: 2021-06-29