Viscolin, a new chalcone from Viscum coloratum, inhibits human neutrophil superoxide anion and elastase release via a cAMP-dependent pathway.

Abstract

The mistletoe Viscum coloratum is used in traditional Chinese medicine to treat inflammatory diseases. In this study, a cellular model in isolated human neutrophils, which are important in the pathogenesis of rheumatoid arthritis, chronic obstructive pulmonary disease, and other inflammatory diseases, was established to elucidate the anti-inflammatory functions of V. coloratum. The partially purified extract of V. coloratum (PPE-SVC) potently inhibited formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced superoxide anion generation and elastase release in a concentration-dependent manner with IC(50) values of 0.58+/-0.03 and 4.93+/-0.54 microg/ml, respectively. Furthermore, a new chalcone derivative, viscolin (4',4''-dihydroxy-2',3',6',3''-tetramethoxy-1,3-diphenylpropane), was isolated from PPE-SVC. Viscolin was demonstrated to inhibit superoxide anion generation and elastase release, as well as to accelerate resequestration of cytosolic calcium in FMLP-activated human neutrophils. Furthermore, the inhibitory effects of viscolin were reversed by protein kinase A (PKA) inhibitor, suggesting that PKA mediates the viscolin-caused inhibitions. Viscolin induced a substantial increase in cAMP levels, and that occurred through the inhibition of phosphodiesterase (PDE) activity but not an increase in adenylate cyclase function. Consistent with this, viscolin potentiated the PGE(1)-caused inhibition of superoxide anion release and calcium mobilization, as well as elevation of cAMP formation. These results demonstrate that inhibition of inflammatory responses in human neutrophils by viscolin is associated with an elevation of cellular cAMP through inhibition of PDE. Comparable results were also observed by PPE-SVC, indicating that the effect of PPE-SVC is at least partly mediated by viscolin. In summary, viscolin is a novel inhibitor of PDE and might be useful for treatment of neutrophilic inflammation.

• Authors: Tsong-Long Hwang, Yann-Lii Leu, Shu-Hui Kao, Ming-Chi Tang, Han-Lin Chang
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 41 Issue 9 Pg. 1433-41 (Nov 01 2006) ISSN: 0891-5849 [Print] United States
• PMID: 17023270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biphenyl Compounds
• viscolin
• Superoxides
• N-Formylmethionine Leucyl-Phenylalanine
• formylmethionyl-leucyl-phenylalanine methyl ester
• Cyclic AMP
• Pancreatic Elastase
• Calcium
• Propane

Topics

• Biphenyl Compounds (pharmacology)
• Calcium (metabolism)
• Chemotaxis, Leukocyte
• Cyclic AMP (metabolism)
• Cytosol (metabolism)
• Humans
• N-Formylmethionine Leucyl-Phenylalanine (analogs & derivatives, pharmacology)
• Neutrophils (drug effects, metabolism)
• Pancreatic Elastase (metabolism)
• Propane (analogs & derivatives, pharmacology)
• Signal Transduction (drug effects)
• Superoxides (metabolism)
• Viscum (chemistry, metabolism)