Ursolic acid enhances nitric oxide and tumor necrosis factor‐α production via nuclear factor‐κB activation in the resting macrophages

摘要

>Ursolic acid (UA), a pentacyclic triterpene acid, is reported to have anti-tumor activities; however, the mechanism underlying its anti-tumorigenic effects is poorly understood. To further determine the mechanism of UA, we investigated the effects of UA on the release of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), and on the level of inducible nitric oxide synthase (iNOS) and TNF-α gene expression in mouse resting macrophages. We found that UA elicited a dose-dependent increase in NO and TNF-α production, and the level of iNOS and TNF-α mRNA. Transient expression and electrophoretic mobility shift assays with nuclear factor-κB (NF-κB) binding sites revealed that the increased level of iNOS mRNA and TNF-α mRNA induced by UA were mediated by the NF-κB transcription factor complex. These results demonstrate that UA stimulates NO and TNF-α release and is able to upregulate iNOS and TNF-α expression through NF-κB transactivation in the resting macrophages.