Ursolic acid enhances nitric oxide and tumor necrosis factor-alpha production via nuclear factor-kappaB activation in the resting macrophages.

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-alpha (TNF-alpha), and on the level of inducible nitric oxide synthase (iNOS) and TNF-alpha gene expression in mouse resting macrophages. We found that UA elicited a dose-dependent increase in NO and TNF-alpha production, and the level of iNOS and TNF-alpha mRNA. Transient expression and electrophoretic mobility shift assays with nuclear factor-kappaB (NF-kappaB) binding sites revealed that the increased level of iNOS mRNA and TNF-alpha mRNA induced by UA were mediated by the NF-kappaB transcription factor complex. These results demonstrate that UA stimulates NO and TNF-alpha release and is able to upregulate iNOS and TNF-alpha expression through NF-kappaB transactivation in the resting macrophages.