title: Salvianolic acid B exerts vasoprotective effects through the modulation of heme oxygenase-1 and arginase activities.
abstract: Salvia miltiorrhiza (Danshen), a traditional Chinese herbal medicine, is commonly used for the prevention and treatment of cardiovascular disorders including atherosclerosis. However, the mechanisms responsible for the vasoprotective effects of Danshen remain largely unknown. Salvianolic acid B (Sal B) represents one of the most bioactive compounds that can be extracted from the water-soluble fraction of Danshen. We investigated the effects of Danshen and Sal B on the inflammatory response in murine macrophages. Danshen and Sal B both induced the expression of heme oxygenase-1 (HO-1) and inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Inhibition of HO activity using Sn-protoporphyrin-IX (SnPP) abolished the inhibitory effect of Sal B on NO production and iNOS expression. Sal B increased macrophage arginase activity in a dose-dependent manner and diminished LPS-inducible tumor necrosis factor-α production. These effects were also reversed by SnPP. These data suggest that HO-1 expression plays an intermediary role in the anti-inflammatory effects of Sal B. In contrast to the observations in macrophages, Sal B dose-dependently inhibited arginase activity in murine liver, kidney, and vascular tissue. Furthermore, Sal B increased NO production in isolated mouse aortas through the inhibition of arginase activity and reduction of reactive oxygen species production. We conclude that Sal B improves vascular function by inhibiting inflammatory responses and promoting endothelium-dependent vasodilation. Taken together, we suggest that Sal B may represent a potent candidate therapeutic for the treatment of cardiovascular diseases associated with endothelial dysfunction.
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sena
authors.initials: S
authors.lastname: Kim
authors.forename: Md Jamal
authors.initials: MJ
authors.lastname: Uddin
authors.forename: Chul
authors.initials: C
authors.lastname: Park
authors.forename: Do Gon
authors.initials: DG
authors.lastname: Ryu
authors.forename: Shin Sung
authors.initials: SS
authors.lastname: Kang
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Ryoo
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Ryter
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Hun Taeg
authors.initials: HT
authors.lastname: Chung
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D005343:Fibrinolytic Agents / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010618:Phenanthrolines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027561:Salvia miltiorrhiza / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014652:Vascular Diseases / Q000517:prevention & control; D053630:Depsides
chemical_list: D001119:Arginase; D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D005343:Fibrinolytic Agents; D051547:Heme Oxygenase-1; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C028972:dan-shen root extract; C076944:salvianolic acid B; D053630:Depsides; C496317:Nos2 protein, mouse