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

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Capsaicin (CPS) exerts many pharmacological effects, but any possible influence on liver fibrosis remains unclear. Therefore, we evaluated the inhibitory effects of CPS on dimethylnitrosamine (DMN) and TGF-β1-induced liver fibrosis in rats and hepatic stellate cells (HSCs). CPS inhibited DMN-induced hepatotoxicity, NF-κB activation, and collagen accumulation. CPS also suppressed the DMN-induced increases in α-SMA, collagen type I, MMP-2, and TNF-α. In addition, CPS inhibited DMN-induced TGF-β1 expression (from 2.3 ± 0.1 to 1.0 ± 0.1) and Smad2/3 phosphorylation (from 1.5 ± 0.1 to 1.1 ± 0.1 and from 1.6 ± 0.1 to 1.1 ± 0.1, respectively) by activating Smad7 expression (from 0.1 ± 0.0 to 0.9 ± 0.1) via PPAR-γ induction (from 0.2 ± 0.0 to 0.8 ± 0.0) (p < 0.05). Furthermore, in HSCs, CPS inhibited the TGF-β1-induced increases in α-SMA and collagen type I expression, via PPAR-γ activation. These results indicate that CPS can ameliorate hepatic fibrosis by inhibiting the TGF-β1/Smad pathway via PPAR-γ activation.

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