Inhibitory effect of betulinic acid on TNF‐α‐induced adhesion molecule and its related signaling

Abstract

Vascular inflammation is an important event in the development of vascular diseases including atherosclerosis. In the present study, we investigated whether betulinic acid (BA) inhibits vascular inflammation process induced by tumor necrosis factor‐alpha (TNF‐α) in human umbilical vein endothelial cells (HUVEC). Pretreatment with BA was significantly blocked TNF‐α‐induced expression levels of cell adhesion molecules such as vascular cell adhesion molecule‐1 (VCAM‐1), intracellular adhesion molecule‐1 (ICAM‐1), and endothelial cell selectin (E‐selectin). Gelatin zymography results showed that TNF‐α‐induced metalloproteinase (MMP)‐2 and MMP‐9 activities were prevented by pretreatment with BA. Real time qRT‐PCR data also showed that BA suppressed TNF‐α‐induced increase in VCAM‐1, ICAM‐1, and E‐selectin mRNA expression levels. In addition, BA inhibited the TNF‐α‐induced intracellular reactive oxygen species (ROS) production. Furthermore, pretreatment with BA significantly inhibited the translocation to nucleus and transcriptional activity of NF‐κB increased by TNF‐α. In conclusion, the present data suggested that BA could suppress TNF‐α‐induced vascular inflammatory process, due to the inhibition of ROS and NF‐κB activation in HUVEC.