This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, W.-J. Articles by Binder, B. R. Search for Related Content PubMed PubMed Citation Articles by Zhang, W.-J. Articles by Binder, B. R.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:465-474.)
© 1997 American Heart Association, Inc.

Articles

Notoginsenoside R1 Counteracts Endotoxin-Induced Activation of Endothelial Cells In Vitro and Endotoxin-Induced Lethality in Mice In Vivo

Wei-Jian Zhang; Johann Wojta; ; Bernd R. Binder

From the Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria (W-J.Z., J.W., B.R.B.), and the Department of Physiology, Beijing University of Traditional Chinese Medicine, PRC (W-J.Z.).

Abstract In this study we investigated a possible counteracting activity of notoginsenoside R1 (NG-R1) on lipopolysaccharide (LPS)-induced effects in vitro and in vivo. The upregulation of plasminogen activator inhibitor-1 (PAI-1) antigen due to LPS (1 µg/mL for 12 hours) in human umbilical vein endothelial cells (HUVECs) was prevented when the cells were incubated simultaneously with 100 µg/mL NG-R1 (PAI-1 antigen: LPS-treated cells, 969±54 ng/10⁵ cells; control cells, 370±15 ng/10⁵ cells; LPS+NG-R1–treated cells, 469±29 ng/10⁵ cells; n=6). The 2.5- and 3.4-fold (2.2- and 3.2-kb) increases in PAI-1 mRNA levels induced by LPS (1 µg/mL for 6 hours) were reduced to 1.4- and 2.6-fold increases in the presence of both LPS and 100 µg/mL NG-R1. LPS-induced tissue factor (TF) activity in HUVECs was also counteracted when the cells were coincubated with both LPS and 100 µg/mL NG-R1 for 6 hours (TF activity: LPS-treated cells, 88.6±6.5 mU/10⁶ cells; control cells, 0.7±0.01 mU/10⁶ cells; LPS+NG-R1–treated cells, 56.0±1.9 mU/10⁶ cells). The 26-fold increase in TF mRNA levels induced by LPS (1 µg/mL for 2 hours) was reduced to a 13-fold increase in the presence of both LPS and 100 µg/mL NG-R1. PAI activity levels in the plasma of mice 4 hours after injection of LPS (10 ng/g body wt) increased 2.3-fold compared with a control group. In contrast, PAI activity from LPS+NG-R1 (1 µg/g body wt NG-R1)–treated animals was at control level (PAI-1 activity: LPS-treated group, 11.3±3.1 U/mL; control group, 4.9±0.3 U/mL; LPS+NG-R1–treated group, 4.3±1.0 U/mL; n=5 to 8). The production of TNF- induced by 1 µg/mL LPS by cultured human whole-blood cells was inhibited by 46% when the cells were incubated together with 100 µg/mL NG-R1. NG-R1 protected mice from the lethal effects of LPS. The 78% lethality induced by LPS/galactosamine was reduced to 23% when NG-R1 was administered simultaneously (P<.01 by ² test). To extend this study to inflammatory cells, the effect of NG-R1 on LPS stimulation of the monocytic cell line THP-1 was investigated. NG-R1 inhibited the LPS-induced degradation of IB- and superinduced LPS-induced IB- mRNA, indicating that the effect of NG-R1 is not restricted to endothelial cells and is at least in part mediated by interference with the NF-B/IB- pathway.

Key Words: notoginsenoside R1 • PAI-1 • tissue factor • endotoxin • TNF-

This article has been cited by other articles:

				Y. M. Schichl, U. Resch, R. Hofer-Warbinek, and R. de Martin Tristetraprolin Impairs NF-{kappa}B/p65 Nuclear Translocation J. Biol. Chem., October 23, 2009; 284(43): 29571 - 29581. [Abstract] [Full Text] [PDF]

				M. Zhang, S.-h. Zhou, S.-P. Zhao, Q.-m. Liu, X.-p. Li, and X.-Q. Shen Irbesartan attenuates Ang II-induced BMP-2 expression in human umbilical vein endothelial cells Vascular Medicine, August 1, 2008; 13(3): 239 - 245. [Abstract] [PDF]

				R. Silverstein Review: D-Galactosamine lethality model: scope and limitations Innate Immunity, June 1, 2004; 10(3): 147 - 162. [Abstract] [PDF]

				W.-J. Zhang and B. Frei Albumin selectively inhibits TNF{alpha}-induced expression of vascular cell adhesion molecule-1 in human aortic endothelial cells Cardiovasc Res, September 1, 2002; 55(4): 820 - 829. [Abstract] [Full Text] [PDF]

				J. Wojta, C. Kaun, G. Zorn, M. Ghannadan, A. W. Hauswirth, W. R. Sperr, G. Fritsch, D. Printz, B. R. Binder, G. Schatzl, et al. C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils Blood, June 28, 2002; 100(2): 517 - 523. [Abstract] [Full Text] [PDF]

				B. R. Binder, G. Christ, F. Gruber, N. Grubic, P. Hufnagl, M. Krebs, J. Mihaly, and G. W. Prager Plasminogen Activator Inhibitor 1: Physiological and Pathophysiological Roles Physiology, April 1, 2002; 17(2): 56 - 61. [Abstract] [Full Text] [PDF]

				W.-J. ZHANG and B. FREI {alpha}-Lipoic acid inhibits TNF-{alpha}-induced NF-{kappa}B activation and adhesion molecule expression in human aortic endothelial cells FASEB J, November 1, 2001; 15(13): 2423 - 2432. [Abstract] [Full Text] [PDF]

				P. Oeth, J. Yao, S.-T. Fan, and N. Mackman Retinoic Acid Selectively Inhibits Lipopolysaccharide Induction of Tissue Factor Gene Expression in Human Monocytes Blood, April 15, 1998; 91(8): 2857 - 2865. [Abstract] [Full Text] [PDF]