A sesquiterpene, dehydrocostus lactone, inhibits the expression of inducible nitric oxide synthase and TNF-alpha in LPS-activated macrophages

Nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) are the major mediators produced in activated macrophages which contribute to the circul atory failure associated with septic shock. A sesquiterpene lactone compoun d (dehydrocostus lactone) isolated from the medicinal plant, Saussurea lapp a, inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW 264.7 cells by suppressing inducible nitric oxide synthase enzyme expressi on. This compound also decreased the TNF-alpha level in LPS-activated syste ms in vitro and in vivo. Thus, dehydrocostus lactone may be a possible cand idate for the development of new drugs to treat endotoxemia accompanied by the overproduction of NO and TNF-alpha.