title: Aqueous extract of Salvia miltiorrhiza attenuates increased endothelial permeability induced by tumor necrosis factor-alpha.
abstract: Salvia miltiorrhiza Bunge, a traditional Chinese herbal medicine, is often used for prevention and treatment of cardiovascular disorders such as atherosclerosis. To understand its mechanism of pharmacological action, its effects on endothelial monolayer permeability are studied. The present study demonstrated that extract of S. miltiorrhiza (ESM) and its major ingredients, Danshensu (DSS) and salvianolic acid B (Sal B), inhibited tumor necrosis factor (TNF-alpha) induced endothelial permeability, whereas the other major ingredient, protocatechualdehyde, was ineffective. ESM, DSS and Sal B also repressed expression of vascular endothelial growth factor (VEGF) and extracellular signal-regulated kinase (ERK) activation in TNF-alpha induced HUVEC cells. Furthermore, it was found that ESM attenuated the disorganization of vascular endothelial (VE)-cadherin induced by TNF-alpha. The effect of ESM on TNF-alpha induced endothelial permeability and redistribution of VE-cadherin is likely due to a reduction of VEGF protein expression as a result of modulation of the ERK signaling pathway. Endothelial cell hyperpermeability is implicated in inflammation and subsequent ischemic reperfusion injury and atherosclerosis. Data from this study suggest that one of the mechanisms S. miltiorrhiza exerts its pharmacological effect is through its modulation of endothelial cell permeability.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, P.O. Box 6888, Tianjin 300072, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ding
authors.forename: Ting-Xiang
authors.initials: TX
authors.lastname: Ye
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Zhao
authors.forename: Ying-Jin
authors.initials: YJ
authors.lastname: Yuan
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Guo
mesh_terms: D001547:Benzaldehydes / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002396:Catechols / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007773:Lactates / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D053630:Depsides
chemical_list: D001547:Benzaldehydes; D001572:Benzofurans; D015820:Cadherins; D002396:Catechols; D048049:Extracellular Signal-Regulated MAP Kinases; D007773:Lactates; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C035055:3,4-dihydroxyphenyllactic acid; C005581:protocatechualdehyde; C076944:salvianolic acid B; D053630:Depsides