RESUMO
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.
Assuntos
Apoptose/efeitos dos fármacos , Citotoxinas/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Peróxido de Hidrogênio/farmacologia , Fármacos Neuroprotetores/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática , Humanos , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Proteína Quinase 8 Ativada por Mitógeno/fisiologia , Proteína Quinase 9 Ativada por Mitógeno/fisiologia , Neuroblastoma , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Eight new prenylated flavonoids, ugonins M-T (1-8), together with five known compounds, ugonins J-L (9-11), 5,4'-dihydroxy-4'',4''-dimethyl-5''-methyl-5''H-dihydrofurano[2'',3'':6,7]flavanone, and quercetin, were isolated and purified from the rhizomes of Helminthostachys zeylanica. The structures of the new isolates were elucidated by spectroscopic and chemical methods. Compounds 1, 3, 5, 7, 8, and 11 showed inhibition of superoxide anion generation and elastase release by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (FMLP/CB).