Protective effect of Bu-7, a flavonoid extracted from Clausena lansium, against rotenone injury in PC12 cells

• Published in: Acta pharmacologica Sinica 2011-11, Vol.32 (11), p.1321-1326
• Main Authors: Li, Bo-yu, Yuan, Yu-he, Hu, Jin-feng, Zhao, Qing, Zhang, Dong-ming, Chen, Nai-hong
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cell Survival - drug effects; Clausena - chemistry; Flavonoids - isolation & purification; Flavonoids - pharmacology; Immunology; Insecticides - adverse effects; Internal Medicine; Medical Microbiology; Membrane Potential, Mitochondrial - drug effects; Original; original-article; p38丝裂原活化蛋白激酶; Parkinson Disease, Secondary - drug therapy; PC12 Cells; PC12细胞; Pharmacology/Toxicology; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Rats; Rotenone - adverse effects; Vaccine; 保护作用; 类黄酮; 线粒体膜电位; 细胞损伤; 鱼藤酮; 黄皮
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2011.119

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 phosphoryla- tion 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 pmol/L） significantly reduced the cell viability in a concentration-dependent manner. Pretreatment with Bu-7 （0.1 and 10 pmol/L） prevented PC12 cells from rotenone injury, whereas Bu-7 （1 pmol/L） had no significant effect. Pretreatment with Bu-7 （0.1 and 10 pmol/L） decreased rotenone-induced apoptosis, attenuated rotenone-induced mitochondrial potential reduction and suppressed rotenone-induced protein phosphorylation and expression, whereas Bu-7 （1 pmol/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.