Neuroprotective effects of ugonin K on hydrogen peroxide-induced cell death in human neuroblastoma SH-SY5Y cells.
Oxidative stress plays an important role in the pathological processes of various neurodegenerative diseases. Ugonin K, a flavonoid isolated from the rhizomes of Helminthostachys zeylanica, possesses potent antioxidant property. In this study, we investigate the neuroprotective effects of ugonin K on hydrogen peroxide (H(2)O(2))-induced apoptosis in SH-SY5Y cells. Incubation of SH-SY5Y cells with H(2)O(2) for 24 h induced cell death measured with MTT assay. Hoechst 33258 staining confirmed that the reduced cell viability by H(2)O(2) was due to apoptosis. In addition, H(2)O(2) increased the expression of 17-kDa cleaved fragment of caspase-3 which could be reversed by pretreatment with ugonin K. Pretreatment with ugonin K attenuated H(2)O(2)-induced cell death in a dose-dependent manner. Neuroprotective effect of ugonin K was abolished by ERK and PI3K inhibitors. Pretreatment with JNK kinase and p38 MAPK inhibitors had no effect on ugonin K-mediated protection against H(2)O(2)-induced apoptosis. Western blotting with anti-phospho-ERK1/2 and anti-phospho-Akt (pS473) antibodies showed that ugonin K increased both ERK1/2 and Akt phosphorylation. These results suggest that ugonin K by activation of ERK1/2 and PI3K/Akt signal pathways protects SH-SY5Y cells from H(2)O(2)-induced apoptosis.
Lin
Yi-Chien
YC
Graduate Institute of Pharmaceutic Chemistry, China Medical University, Taichung, Taiwan.
Huang
Yaun-Chao
YC
Chen
Sheng-Chih
SC
Liaw
Chih-Chuang
CC
Kuo
Sheng-Chu
SC
Huang
Li-Jiau
LJ
Gean
Po-Wu
PW
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology; D048056:Mitogen-Activated Protein Kinase 9 / Q000502:physiology; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D003603:Cytotoxins; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D018696:Neuroprotective Agents; C540912:ugonin K; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D048056:Mitogen-Activated Protein Kinase 9; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D053148:Caspase 3