Effect of Paeotang on tumor necrosis factor α-induced vascular inflammation in human umbilical vein endothelial cells.

Abstract

To investigate whether Paeotang (10-50 μg/mL) suppresses tumor necrosis factor α (TNF-α)-induced vascular inflammatory processes in human umbilical vein endothelial cells (HUVEC). The ingredients composed of Paeotang include Glycyrrhiza glabra, Zingiber officinale, Cinnamomum zeylanuicum, Salvia miltiorrhiza, Prunus persica, Paeonia szechuanica, Poria cocos and Cynanchum wilfordii. Herbs were mixed according to equal ratio of weight and ground into a crude powder. The effect of Paeotang on the expression of cell adhesion molecules and protective role in HUVEC stimulated by TNF-α were evaluated. Pretreatment with Paeotang decreased TNF-α-induced adhesion of HL-60 monocytic cells, as well as protein and mRNA expressions of intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial-selectin (E-selectin). Paeotang also dose-dependently inhibited TNF-α-induced matrix metalloproteinase-2 and -9 expressions. Paeotang significantly decreased TNF-α-induced intracellular reactive oxygen species (ROS) production. The Western blot and immunofluorescence analysis showed that Paeotang suppressed the translocation of p65 nuclear factor κB (NF-κB) to the nucleus. In addition, Paeotang inhibited the TNF-α-induced degradation of NF-κB inhibitor α (IκB-α) and by inhibiting the phosphorylation of IκB-α. Furthermore, pretreatment of Paeotang increased the heme oxygenase 1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2) protein expression in HUVECs stimulated TNF-α. HO-1 was inhibited by Sn-protoporphyrin, HO-1 inhibitor, and increased by cobalt protopophyrin, HO-1 inducer. Furthermore, HO-1 induction was increased by single processing of Paeotang in a dose-dependent manner. These data suggest that Paeotang might be a benefificial therapeutic in vascular inflflammation through regulation of Nrf2-mediated HO-1 expression and inhibition of ROS/NF-κB signaling pathway. Thus, Paeotang maybe serve as a potential anti-atherogenic agent.