Expression of inducible nitric oxide synthase by α-hederin in macrophages

alpha-Hederin, a triterpene saponin, is reported to have antitumor activities: however, the mechanism underlying its therapeutic effects is not known. In this study, we examine the effects of alpha-hederin on the release of nitric oxide (NO) and the level of inducible nitric oxide synthase (iNOS) gene expression in mouse macrophages. alpha-Hederin elicited a dose-dependent increase in NO secretion. Reverse-transcription polymerase chain reaction showed that the increased NO secretion was due to an increase in iNOS mRNA. Transient expression assays with NF-kappaB binding sites linked to the luciferase gene revealed that the increased level of iNOS mRNA induced by alpha-hederin was mediated by the NF-kappaB transcription factor complex. These results demonstrate that alpha-hederin stimulates NO release and is able to upregulate iNOS expression through NF-kappaB transactivation, which may be a mechanism, whereby alpha-hederin elicits its biological effects.