Triptolide Alleviates Oxidized LDL-Induced Endothelial Inflammation by Attenuating the Oxidative Stress-Mediated Nuclear Factor-Kappa B Pathway

Abstract

Background

Endothelial inflammation triggered by oxidized LDL (ox-LDL) is a crucial mechanism involved in atherosclerosis. Triptolide (TP), a primary active ingredient of the traditional Chinese medicine Tripterygium wilfordii Hook F, possesses antioxidant and anti-inflammatory properties in vivo. However, limited information is available regarding these effects on endothelial inflammation occurring in atherosclerosis.

Objectives

This study investigated the effects and possible mechanisms of action of TP on ox–LDL-induced inflammatory responses in human umbilical vein endothelial cells.

Methods

Human umbilical vein endothelial cells were preincubated with TP at the indicated concentrations for 1 hour and then incubated with ox-LDL (50 µg/mL) for the indicated times.

Results

Preincubation of cultured human umbilical vein endothelial cells with TP inhibited ox–LDL-induced cytokine and chemokine production, adhesion molecule expression, and monocyte adhesion in a concentration-dependent manner. The concentrations of 8-isoprostane, malondialdehyde, and superoxide increased after human umbilical vein endothelial cells were exposed to ox-LDL, which were associated with decreased activities of total superoxide dismutase and its isoenzyme (ie, CuZn- superoxide dismutase). Preincubation with TP reversed ox–LDL-induced effects in all events. Moreover, preincubation with TP also attenuated ox–LDL-induced nuclear factor-kappa B transcriptional activation in a concentration-dependent manner, via the suppression of inhibitor of kappa Balpha (IκBα) phosphorylation and subsequent nuclear factor-kappa B DNA binding.

Conclusions

These data indicate that TP inhibits ox–LDL-induced endothelial inflammation, possibly via suppression of the oxidative stress-dependent activation of the nuclear factor-kappa B signaling pathway.