title: Effects of flavonoids isolated from scutellariae radix on the production of tissue-type plasminogen activator and plasminogen activator inhibitor-1 induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells.
abstract: The effects of different flavonoids isolated from the roots of Scutellaria baicalensis Georgi on the production of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) induced by thrombin and thrombin receptor agonist peptide, Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe, have been examined in cultured human umbilical vein endothelial cells (HUVECs). Thrombin and thrombin receptor agonist peptide induced production of both t-PA and PAI-1 and the elevation of intracellular free calcium concentration ([Ca2+]i). Baicalein isolated from Scutellariae Radix dose-dependently inhibited PAI-1 production induced by thrombin and thrombin receptor agonist peptide; its concentrations for 50% inhibition (IC50) were 6.8 and 3.5 microM, respectively. Other flavonoids had no effect. In contrast, flavonoids isolated from Scutellariae Radix had no effect on production of t-PA induced by thrombin and thrombin receptor agonist peptide. Baicalein inhibited the elevation of [Ca2+]i induced by thrombin and thrombin receptor agonist peptide and, at a concentration of 1000 microM, slightly increased t-PA production. These findings suggest that the mechanism by which baicalein inhibits PAI-1 production induced by thrombin and thrombin receptor agonist peptide might be by reduction of [Ca2+]i elevation. The results suggest that baicalein in Scutellariae Radix might be active as a drug in the treatment of arteriosclerosis and thrombosis.
authors.affiliation: 2nd Department of Medical Biochemistry, School of Medicine, Ehime University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Yokoi
authors.forename: N
authors.initials: N
authors.lastname: Matsushita
authors.forename: H
authors.initials: H
authors.lastname: Okuda
mesh_terms: D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D018179:Receptors, Thrombin / Q000819:agonists; D013917:Thrombin / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D010446:Peptide Fragments; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D018179:Receptors, Thrombin; C072032:thrombin receptor peptide (42-55); C006680:baicalein; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D002118:Calcium