Piceatannol-3'-O-beta-D-glucopyranoside as an active component of rhubarb activates endothelial nitric oxide synthase through inhibition of arginase activity.
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 IC((50)) 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.
Woo
Ainieng
A
Department of Biology, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea.
Min
Byungsun
B
Ryoo
Sungwoo
S
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012250:Rheum / Q000737:chemistry*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
D005960:Glucosides; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D013267:Stilbenes; C554087:piceatannol-3'-O-glucopyranoside; D009569:Nitric Oxide; C041525:3,3',4,5'-tetrahydroxystilbene; D052250:Nitric Oxide Synthase Type III; D001119:Arginase