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

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Abstract
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.