The nitric oxide-producing properties of Ulmi radicis cortex extract

We investigated the effect of Ulmi radicis cortex extract (UrCE) on the production of nitric oxide (NO). Stimulation of mouse peritoneal macrophages with UrCE after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in the increased NO synthesis. UrCE had no effect on NO synthesis by itself. When UrCE was used in combination with rIFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of UrCE on NO synthesis was shown 6 h after treatment with rIFN-gamma. NO production was inhibited by N-G-monomethyl-L-arginine. The increased production of NO from rIFN-gamma plus UrCE-stimulated cells was decreased by the treatment of protein kinase C inhibitor such as staurosporin. In addition, synergy between rIFN-gamma and UrCE was mainly dependent on UrCE-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the preparations of UrCE were endotoxin free. These results suggest that the capacity of UrCE to increase NO production from rIFN-gamma-primed mouse peritoneal macrophages is the result of UrCE-induced TNF-alpha secretion.