Inhibition of the transcription factor NF-kappa B by sesquiterpene lactones from Podachaenium eminens

Investigation of Podachaenium eminens afforded nine sesquiterpene lactones (Sls) from which costunolide, 7-hydroxycostunolide, santamarin as well as 3 -chlorodehydroleucodin are new for this plant and 3,4-dehydro-4-dehydroxypo dachaenin (= 3-costoyloxydehydroleucodin) is found for the first time in na ture. All isolated Sis were studied for their anti-inflammatory activity us ing the transcription factor NF-kappaB as a molecular target. NF-kappaB is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. Except for podachaenin, all compounds completely inhibited NF-k appaB DNA binding in an electrophoretic mobility shift assay at concentrati ons between 5 and 200 muM without showing any cytotoxic effects. 3,4-Epoxyd ehydroleucodin possessing an alpha -methylene-gamma -butyrolactone and a se cond reactive structure element by its epoxy ring alpha,beta to a carbonyl group was most active. Although the majority of the Sis tested in this stud y were monofunctional only low concentrations of 50 muM were often needed f or complete inhibition. Possible reasons are discussed for this result.