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Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability / 中华医学杂志(英文版)
Chinese Medical Journal ; (24): 1737-1743, 2016.
Article in English | WPRIM | ID: wpr-251313
ABSTRACT
<p><b>BACKGROUND</b>Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability.</p><p><b>METHODS</b>Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers.</p><p><b>RESULTS</b>A total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 μmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 μmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture.</p><p><b>CONCLUSIONS</b>The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Rheum / Capillary Permeability / Drugs, Chinese Herbal / Cadherins / Cell Line / Chemistry / Matrix Metalloproteinase 9 / Cell Biology / Cell Proliferation Limits: Humans Language: English Journal: Chinese Medical Journal Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Rheum / Capillary Permeability / Drugs, Chinese Herbal / Cadherins / Cell Line / Chemistry / Matrix Metalloproteinase 9 / Cell Biology / Cell Proliferation Limits: Humans Language: English Journal: Chinese Medical Journal Year: 2016 Type: Article