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 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-alpha 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-alpha by lipopolysaccharide (LPS)-activated macrophages from the results of bioassay (IC(50) values of 1 and 2 are 12.3 and 310.5 microM, 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-alpha production.
Jang
M K
MK
Sohn
D H
DH
Ryu
J H
JH
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D001681:Biological Assay; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D018514:Plant Structures / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D030521:Zingiberaceae / Q000737:chemistry*
C438915:1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010636:Phenols; D010936:Plant Extracts; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C438916:procurcumenol; D003474:Curcumin