TY - JOUR
T1 - Viscolin, a new chalcone from Viscum coloratum, inhibits human neutrophil superoxide anion and elastase release via a cAMP-dependent pathway
AU - Hwang, Tsong Long
AU - Leu, Yann Lii
AU - Kao, Shu Hui
AU - Tang, Ming Chi
AU - Chang, Han Lin
PY - 2006/11/1
Y1 - 2006/11/1
N2 - 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 IC50 values of 0.58 ± 0.03 and 4.93 ± 0.54 μg/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 PGE1-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.
AB - 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 IC50 values of 0.58 ± 0.03 and 4.93 ± 0.54 μg/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 PGE1-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.
KW - Elastase
KW - Neutrophil
KW - Superoxide
KW - Viscolin
KW - Viscum coloratum
KW - cAMP
UR - http://www.scopus.com/inward/record.url?scp=33749049578&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2006.08.001
DO - 10.1016/j.freeradbiomed.2006.08.001
M3 - 文章
C2 - 17023270
AN - SCOPUS:33749049578
SN - 0891-5849
VL - 41
SP - 1433
EP - 1441
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 9
ER -