Pristimerin, a natural anti-tumor triterpenoid, inhibits LPS-induced TNF-α and IL-8 production through down-regulation of ROS-related classical NF-κB pathway in THP-1 cells

Pristimerin, a naturally occurring quinonemethide triterpenoid compound, is known to exert a variety of pharmacological activities. In the present study, we investigated the molecular actions of pristimerin against LPS-induced inflammatory responses in human monocytic THP-1 cells. The results showed that pristimerin inhibited the production of TNF-α and IL-8 in a dose-dependent manner. To explore the possible mechanisms underlying these inhibitions by pristimerin, we examined the intracellular ROS level and the NF-κB protein signaling pathway. Pristimerin clearly scavenged LPS-induced intracellular ROS production. In addition, pristimerin prevented LPS-induced NF-κB activation through the inhibition of phosphorylation of IKKα/β, phosphorylation and degradation of IκBα, as well as phosphorylation and nuclear translocation of NF-κB p65. These findings suggest that pristimerin down-regulates the expression of pro-inflammatory mediators through blocking of NF-κB activation by inhibiting interconnected ROS/IKK/NF-κB signaling pathways.