6,7-di-O-glucopyranosyl-esculetin protects SH-SY5Y cells from dopamine-induced cytotoxicity.
Dopamine, as a neurotoxin, can elicit severe Parkinson's disease-like syndrome by elevating intracellular reactive oxygen species levels and apoptotic activity. In this study, we examined the effect of 6,7-di-O-glucopyranosyl-esculetin, which was extracted from Fraxinus sieboldiana bloom, on dopamine-induced cytotoxicity and the underlying mechanism in human neuroblastoma SH-SY5Y cells. Our results suggest that the protective effects of 6,7-di-O-glucopyranosyl-esculetin (0.1, 1 and 10 microM) on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing reactive oxygen species levels, and its anti-apoptotic effect via protecting mitochondrion membrane potential (Delta Psi m), enhancing superoxide dismutaese (SOD) activity and reduced glutathione (GSH) levels, and regulating p53, Bax and Bcl-2 expression. In addition, 6,7-di-O-glucopyranosyl-esculetin inhibited the release of cytochrome c and apoptosis-inducing factor (AIF), and the protein expression of activated caspase 3. These data indicate that 6,7-di-O-glucopyranosyl-esculetin may provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Parkinson's disease.
Zhao
Da-Long
DL
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine affiliated Ministry of Education, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Zou
Li-Bo
LB
Lin
Sheng
S
Shi
Jian-Gong
JG
Zhu
Hai-Bo
HB
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D031661:Fraxinus / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D024301:Plant Bark / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014468:Umbelliferones / Q000302:isolation & purification / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C529172:6,7-di-O-glucopyranosylesculetin; D005960:Glucosides; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D014468:Umbelliferones; D051028:bcl-2-Associated X Protein; D013482:Superoxide Dismutase; D053148:Caspase 3; D004298:Dopamine