Effect of notoginsenoside R1 on the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in cultured human umbilical vein endothelial cells.

Abstract

Among other Chinese herb drugs, Panax notoginseng is used to treat cardiovascular diseases. To elucidate any possible effects of this drug on the hemostatic system in vitro, we analyzed the influence of one of its major active constituents on fibrinolytic parameters of cultured human umbilical vein endothelial cells (HUVECs). When confluent cultures of HUVECs (passages 2 to 3) were conditioned with purified notoginsenoside R1 (NR1), a dose- (0.01 to 100 micrograms NR1/mL) and time-dependent increase in tissue-type plasminogen activator (TPA) synthesis was observed, which was significant from 0.1 microgram NR1/mL and from 6 hours of incubation with 100 micrograms NR1/mL on. TPA antigen increased from 3.9 +/- 0.2 ng per 10(5) cells per 24 hours to 8.0 +/- 0.5 ng per 10(5) cells per 24 hours on addition of 100 micrograms NR1/mL. In contrast, no change in urokinase-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) antigen synthesis was seen. There was also no effect of NR1 on PAI-1 deposition in the extracellular matrix. As judged from fibrin autography and reverse fibrin autography, TPA activity and TPA-PAI-1 complexes reached a maximal stimulation of more than threefold and twofold, respectively, at a concentration of 100 micrograms NR1/mL in conditioned media. On the contrary, NR1 induced a more than fivefold decrease in PAI-1 activity at the same concentration of NR1 in conditioned media. On Northern blot analysis of RNA obtained from NR1-stimulated and control HUVECs, NR1 induced a significant increase in TPA mRNA (192% of control value at 100 micrograms NR1/mL) while PAI-1 mRNA remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)