Morroniside prevents peroxide-induced apoptosis by induction of endogenous glutathione in human neuroblastoma cells.
(1) Morroniside belongs to an extensive group of natural iridorid glycosides. In the present study, using human neuroblastoma SH-SY5Y cells, we have investigated the protective effects of this compound on modifications in endogenous reduced glutathione (GSH), intracellular oxygen species (ROS) and apoptotic death on H(2)O(2)-mediated cytoxicity. (2) Incubation of cells with morroniside led to a significant dose-dependent elevation of cellular GSH accompanied by a marked protection against H(2)O(2)-mediated toxicity. Morroniside at 1-100 microM inhibited the formation of ROS and the activation of caspase-3 and 9, and the upregulation of Bcl-2, whereas no significant change occurred in Bax levels. (3) The results indicated that the anti-oxidative and anti-apoptotic properties render this natural compound potentially protective against H(2)O(2)-induced cytotoxicity. (4) This study suggested that intracellular GSH appeared to be an important factor in morroniside-mediated cytoprotection against H(2)O(2)-toxicity in SH-SY5Y cells.
Wang
Wen
W
Department of Pharmacology, Xuan-Wu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China.
Huang
Wenting
W
Li
Lin
L
Ai
Houxi
H
Sun
Fangling
F
Liu
Ci
C
An
Yi
Y
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal; D005978:Glutathione / Q000378:metabolism*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D004365:Drugs, Chinese Herbal; D006027:Glycosides; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C488401:morroniside; D006861:Hydrogen Peroxide; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione