A curcuminoid and sesquiterpenes as inhibitors of macrophage TNF-alpha release from Curcuma zedoaria

Tumor necrosis factor-alpha (TNF-alpha) is one of the major mediators produ ced in activated macrophages which contribute to the circulatory failure as sociated with septic shock. in the course of screening marketed oriental an ti-inflammatory herbal drugs for TNF-alpha antagonistic activity, a crude m ethanolic extract of the rhizomes of Curcuma zedoaria exhibited significant activity. The activity-guided fractionation and repetitive chromatographic procedures with the EtOAc-soluble fraction resulted in the isolation of th ree active compounds. They were identified as 1,7-bis(4-hydroxyphenyl)-1,4, 6-heptatrien-3-one (1). procurcumenol (2) and epiprocurcumenol (3) by spect ral data analysis. They inhibited the production of TNF-a by lipopolysaccha ride (LPS)-activated macrophages from the results of bioassay (IC50 values of 1 and 2 are 12.3 and 310.5 muM, respectively) and Western blot assay. Th ese results imply that the traditional use of C. zedoaria rhizome as anti-i nflammatory drug may be explained at least in part, by the inhibition of TN F-alpha production.