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

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.