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.
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.
Kimura
Y
Y
2nd Department of Medical Biochemistry, School of Medicine, Ehime University, Japan.
Yokoi
K
K
Matsushita
N
N
Okuda
H
H
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
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