Piceatannol-3'-O-beta-D-glucopyranoside as an active component of rhubarb activates endothelial nitric oxide synthase through inhibition of arginase activity
Experimental & Molecular Medicine
;
: 524-532, 2010.
Artigo
em Inglês
| WPRIM
| ID: wpr-214627
ABSTRACT
Arginase competitively inhibits nitric oxide synthase (NOS) via use of the common substrate L-arginine. Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. Here, we demonstrate that piceatannol-3'-O-beta-D-glucopyranoside (PG), a potent component of stilbenes, inhibits the activity of arginase I and II prepared from mouse liver and kidney lysates, respectively, in a dose-dependent manner. In human umbilical vein endothelial cells, incubation of PG markedly blocked arginase activity and increased NOx production, as measured by Griess assay. The PG effect was associated with increase of eNOS dimer ratio, although the protein levels of arginase II or eNOS were not changed. Furthermore, isolated mice aortic rings treated with PG showed inhibited arginase activity that resulted in increased nitric oxide (NO) production upto 78%, as measured using 4-amino-5-methylamino-2',7'-difluorescein (DAF-FM) and a decreased superoxide anions up to 63%, as measured using dihydroethidine (DHE) in the intact endothelium. PG showed IC50 value of 11.22 microM and 11.06 microM against arginase I and II, respectively. PG as an arginase inhibitor, therefore, represents a novel molecule for the therapy of cardiovascular diseases derived from endothelial dysfunction and may be used for the design of pharmaceutical compounds.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Aorta
/
Arginase
/
Rheum
/
Estilbenos
/
Espécies Reativas de Oxigênio
/
Células Endoteliais
/
Relação Dose-Resposta a Droga
/
Ativação Enzimática
/
Óxido Nítrico Sintase Tipo III
/
Glucosídeos
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2010
Tipo de documento:
Artigo
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