Salvianolic acid B attenuates plasminogen activator inhibitor type 1 production in TNF-α treated human umbilical vein endothelial cells

✍ Scribed by Zhe Zhou; Yong Liu; Ai-Dong Miao; Sheng-Qi Wang

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 157 KB
• Volume: 96
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20567

✦ Synopsis

Abstract

Plasminogen activator inhibitor type 1 (PAI‐1), which plays a role in the development of atherosclerosis, is produced by endothelial cells following stimulation with various inflammatory cytokines such as tumor necrosis factor (TNF‐α). In the present study, we investigated the effects of a potent water‐soluble antioxidant, salvianolic acid B (SalB; derived from the Chinese herb, Salvia miltiorrhiza), on the expression of PAI‐1 in TNF‐α‐treated human umbilical vein endothelial cells (HUVECs). We found that SalB inhibited TNF‐α‐induced PAI‐1 mRNA production and protein secretion in HUVECs. Treatment with SalB (0.05 and 0.15 µM) notably attenuated TNF‐α induced expression of PAI‐1 to 90.5% and 74.6%, respectively, after 12 h, and to 75.1% and 64.2%, respectively, after 18 h. We also observed a dose‐dependent decrease in PAI‐1 protein production in the presence of SalB. We then used pathway inhibitors to investigate which step of the TNF‐α induced signaling pathway was targeted by SalB. We found that the c‐Jun N‐terminal kinase (JNK) inhibitor, SP600125, increased the inhibitory effects of SalB on TNF‐α‐induced PAI‐1 secretion, whereas the nuclear factor‐κB (NF‐κB) inhibitor, emodin, and the extracellular signal‐regulated kinase (ERK) inhibitor, PD98059, did not. A gel shift assay further showed that SalB inhibited the TNF‐α‐activated NF‐κB and AP‐1 DNA binding activities in a dose‐dependent manner. Collectively, these results indicate that the NF‐κB and ERK‐AP‐1 pathways are possible targets of SalB in the regulation of TNF‐α‐stimulated PAI‐1 production in HUVECs. © 2005 Wiley‐Liss, Inc.