Activation of inducible nitric oxide synthase by Euonymus alatus in mouse peritoneal macrophages

Background: Euonymus alatus (EA) has been used for tumor therapy. However, it is still unclear how this herb prevents the diseases in experimental models. Nitric oxide (NO) as a potent macrophage-derived effector molecule against a variety of tumors has received increasing attention. Methods: Using mouse peritoneal macrophages, we have examined the mechanism by which EA regulates NO production. Results: When EA was used in combination with recombinant interferon-γ (rIFN-γ), there was a marked cooperative induction of NO production. However, EA had no effect on NO production by itself. The increased production of NO from rIFN-γ plus EA-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappa B (NF-κB). Furthermore, treatment of peritoneal macrophages with rIFN-γ plus EA caused a significant increase in tumor necrosis factor-α (TNF-α) production. PDTC also decreased the effects of EA on TNF-α production significantly. Conclusions: EA increases the production of NO and TNF-α by rIFN-γ-primed macrophages and suggest that NF-κB plays a critical role in mediating these effects of EA.