Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF-alpha-treated human aortic endothelial cells

Attachment to, and migration of leukocytes into the vessel wall is an early event in atherogenesis. Expression of cell adhesion molecules by the arter ial endothelium may play a major role in atherosclerosis. It has been sugge sted that antioxidants inhibit the expression of adhesion molecules and may thus attenuate the processes leading to atherosclerosis. In the present st udy, the effects of a potent water-soluble antioxidant, salvianolic acid B (Sal B), and an aqueous ethanol ic extract (SME), both derived from a Chine se herb, Salvia miltiorrhiza, on the expression of endothelial leukocyte ad hesion molecules by tumor necrosis factor-alpha (TNF-alpha)-treated human a ortic endothelial cells (HAECs) were investigated. When pretreated with SME (50 and 100 mug/ml), the TNF-alpha -induced expression of vascular adhesio n molecule-1 (VCAM-1) was notably attenuated (77.2 +/-3.2% and 80.0 +/-2.2% , respectively); and with Sal B (1, 2 5, 5, 10, and 20 mug/ml), 84.5 +/-1.9 %, 78.8 +/-1.2%, 58.9 +/-0.4%, 58.7 +/-0.9%, and 57.4 +/-0.3%, respectively . Dose-dependent lowering of expression of intercellular cell adhesion mole cule-1 (ICAM-1) was also seen with SME or Sal B. in contrast, the expressio n of endothelial cell selectin (E-selectin) was not affected. SME (50 mug/m l) or Sal B (5 mug/ml) significantly reduced the binding of the human monoc ytic cell line, U937, to TNF-alpha -stimulated HAECs (45.7 +/-2.5% and 55.8 +/-1.2%, respectively). SME or Sal B significantly inhibited TNF-alpha -in duced activation of nuclear factor kappa B (NF-kappaB) in HAECs (0.36- and 0.48-fold, respectively). These results demonstrate that SME and Sal B have anti-inflammatory properties and may explain their anti-atherosclerotic pr operties. This new mechanism of action of Sal B and SME, in addition to the ir previously reported inhibition of LDL, may help explain their efficacy i n the treatment of atherosclerosis. (C) 2001 Wiley-Liss, Inc.