A Curcuminoid and Sesquiterpenes as Inhibitors of Macrophage TNF-α Release from Curcuma zedoaria

Abstract

Tumor necrosis factor-α (TNF-α) is one of the major mediators produced in activated macrophages which contribute to the circulatory failure associated with septic shock. In the course of screening marketed oriental anti-inflammatory herbal drugs for TNF-α antagonistic activity, a crude methanolic 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 three active compounds. They were identified as 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (1), procurcumenol (2) and epiprocurcumenol (3) by spectral data analysis. They inhibited the production of TNF-α by lipopolysaccharide (LPS)-activated macrophages from the results of bioassay (IC₅₀ values of 1 and 2 are 12.3 and 310.5 μM, respectively) and Western blot assay. These results imply that the traditional use of C. zedoaria rhizome as anti-inflammatory drug may be explained at least in part, by the inhibition of TNF-α production.

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