Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 628, Issue 1-3, Pages 155-163Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2009.11.046
Keywords
Catalpol; Hydrogen peroxide; Apoptosis; HUVEC
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Catalpol, an iridoid glucoside found in the root of Rehmannia glutinosa Libosch, has been demonstrated to reduce apoptosis in neuronal cell lines. Recent data suggests that catalpol also exerts anti-apoptotic effects on other cell types. The aim of the present study was to investigate whether catalpol protects against hydrogen peroxide (H2O2) induced apoptosis in human umbilical vein endothelial cells (HUVECs). Apoptotic cells were detected by terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, Annexin V-fluorescein isothiocyanate binding assay and by assessment of caspase-3 activity. The level of intracellular reactive oxygen species was quantified by 2', 7'-dichlorofluorescein diacetate assay. Expression of Akt, Bad, Bcl-2 and Bax mRNA and protein was determined by real-time semiquantitative reverse transcription-polymerase chain reaction and Western blotting. Apoptosis in HUVECs was associated with increased Bax, decreased Bcl-2 activity and inactivated phosphorylation of Akt and Bad after 24 h of H2O2 exposure. Pre-treatment of HUVECs with catalpol significantly reduced H2O2-induced intracellular reactive oxygen species release. Catalpol not only increased the expression of Bcl-2, while decreasing Bax expression, but also induced Akt activation and Bad phosphorylation, and ultimately reduced H2O2-induced apoptosis. The protective effects of catalpol were partially inhibited by the phosphatidylinositol 3-kinase (PI3K) antagonist wortmannin or 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). Taken together. these results suggest that pre-treatment of HUVECs with catalpol can block H(2)O2-induced apoptosis, and that the underlying mechanism involves reactive oxygen species scavenging, activation of the PI3K/Akt-Bad signaling pathway and increased Bcl-2 and decreased Bax expression. (C) 2009 Elsevier B.V. All rights reserved.
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